Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1 α (HIF-1α)/HO-1 signaling pathway.
Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway. Free Radic Biol Med. 2021 Jan 22;: Authors: Li X, Yu J, Gong L, Zhang Y, Dong S, Shi J, Li C, Li Y, Zhang Y, Li H Abstract Sepsis caused acute lung injury (ALI) is a kind of serious disease in critically ill patients with very high morbidity and mortality. Recently, it has been demonstrated that Golgi is involved in the process of oxidative stress. However, whether Golgi stress is associated with oxidative stress in septic ind...
Source: Free Radical Biology and Medicine - January 22, 2021 Category: Biology Authors: Li X, Yu J, Gong L, Zhang Y, Dong S, Shi J, Li C, Li Y, Zhang Y, Li H Tags: Free Radic Biol Med Source Type: research

Epigenomic Regulation by Labile Iron.
Abstract Iron is an essential micronutrient metal for cellular functions but can generate highly reactive oxygen species resulting in oxidative damage. For these reasons its uptake and metabolism is highly regulated. A small but dynamic fraction of ferrous iron inside the cell, termed intracellular labile iron, is redox-reactive and ready to participate multiples reactions of intracellular enzymes. Due to its nature its determination and precise quantification has been a roadblock. However, recent progress in the development of intracellular labile iron probes are allowing the reevaluation of our current understan...
Source: Free Radical Biology and Medicine - January 22, 2021 Category: Biology Authors: Camarena V, Huff TC, Wang G Tags: Free Radic Biol Med Source Type: research

Effects of Albumin, Transferrin and Humic-Like Substances on Iron-Mediated OH Radical Formation in Human Lung Fluids.
Abstract Inhalation of particulate matter is hypothesized to contribute to health effects by overproducing reactive oxygen species (ROS) and inducing oxidative stress. Fe(II) has been shown to contribute to ROS generation in acellular simulated lung fluids. Atmospheric humic-like substances (HULIS) have been shown to chelate Fe(II) and significantly enhance this ROS generation. Here, we investigate Fe(II)-mediated .OH generation from the iron active proteins in lung fluid, albumin and transferrin, fulvic acid, a surrogate for HULIS, in human bronchoalveolar lavage fluid (BALF). We find that albumin enhances .OH ge...
Source: Free Radical Biology and Medicine - January 21, 2021 Category: Biology Authors: Gonzalez DH, Diaz DA, Baumann JP, Ghio AJ, Paulson SE Tags: Free Radic Biol Med Source Type: research

Iron homeostasis and disorders revisited in the sepsis.
Abstract Sepsis is a life-threatening condition caused by a dysregulated host-response to inflammation, although it currently lacks a fully elucidated pathobiology. Iron is a crucial trace element that is essential for fundamental processes in both humans and bacteria. During sepsis, iron metabolism is altered, including increased iron transport and uptake into cells and decreased iron export. The intracellular sequestration of iron limits its availability to circulating pathogens, which serves as a conservative strategy against the pathogens. Although iron retention has been showed to have protective protect effe...
Source: Free Radical Biology and Medicine - January 21, 2021 Category: Biology Authors: Liu Q, Wu J, Zhang X, Wu X, Zhao Y, Ren J Tags: Free Radic Biol Med Source Type: research

MITO-MANAGING ROS & REDOX TO REBOOT THE IMMUNE SYSTEM Tapping Mitochondria & Redox Management to Extend the Reach of Hematopoietic Stem Cell Transplantation.
MITO-MANAGING ROS & REDOX TO REBOOT THE IMMUNE SYSTEM Tapping Mitochondria & Redox Management to Extend the Reach of Hematopoietic Stem Cell Transplantation. Free Radic Biol Med. 2021 Jan 21;: Authors: Mohrin M Abstract Hematopoietic stem cells (HSCs) are responsible for life-long production of blood and immune cells. HSC transplantation (HSCT) is the original cell therapy which can cure hematological disorders but also has the potential to treat other diseases if technical and safety barriers are overcome. To maintain homeostatic hematopoiesis or to restore hematopoiesis during transplantatio...
Source: Free Radical Biology and Medicine - January 21, 2021 Category: Biology Authors: Mohrin M Tags: Free Radic Biol Med Source Type: research

Energy substrate metabolism and mitochondrial oxidative stress in cardiac ischemia/reperfusion injury.
We describe the main metabolites accumulating during ischemia in the glucose, fatty acid, and Krebs cycle pathways. Hyperglycemia, often present in the acute stress condition of ischemia/reperfusion, increases cytosolic ROS concentrations through the activation of NADPH oxidase 2 and increases mitochondrial ROS through the metabolic overloading and decreased binding of hexokinase II to mitochondria. Fatty acid-linked ROS production is related to the increased fatty acid flux and corresponding accumulation of long-chain acylcarnitines. Succinate that accumulates during anoxia/ischemia is suggested to be the main source of R...
Source: Free Radical Biology and Medicine - January 20, 2021 Category: Biology Authors: Dambrova M, Zuurbier CJ, Borutaite V, Liepinsh E, Makrecka-Kuka M Tags: Free Radic Biol Med Source Type: research

Corrigendum to "An exacerbated metabolism and mitochondrial reactive oxygen species contribute to mitochondrial alterations and apoptosis in CD4 T cells during the acute phase of Trypanosoma cruzi infection" [Free Rad. Biol. Med. 163 (2021) 268-280].
Corrigendum to "An exacerbated metabolism and mitochondrial reactive oxygen species contribute to mitochondrial alterations and apoptosis in CD4 T cells during the acute phase of Trypanosoma cruzi infection" [Free Rad. Biol. Med. 163 (2021) 268-280]. Free Radic Biol Med. 2021 Jan 19;: Authors: Ana Y, Rojas Marquez JD, Fozzatti L, Baigorrí RE, Marin C, Maletto BA, Cerbán FM, Radi R, Piacenza L, Stempin CC PMID: 33483208 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 19, 2021 Category: Biology Authors: Ana Y, Rojas Marquez JD, Fozzatti L, Baigorrí RE, Marin C, Maletto BA, Cerbán FM, Radi R, Piacenza L, Stempin CC Tags: Free Radic Biol Med Source Type: research

Corrigendum to "Nrf2-mediated liver protection by esculento side A against acetaminophen toxicity through the AMPK/Akt/GSK3 β pathway" [Free. Radic. Biol. Med. 101(2016)401-412].
Corrigendum to "Nrf2-mediated liver protection by esculento side A against acetaminophen toxicity through the AMPK/Akt/GSK3β pathway" [Free. Radic. Biol. Med. 101(2016)401-412]. Free Radic Biol Med. 2021 Jan 19;: Authors: Wang L, Zhang S, Cheng H, Lv H, Cheng G, Ci X PMID: 33483209 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 19, 2021 Category: Biology Authors: Wang L, Zhang S, Cheng H, Lv H, Cheng G, Ci X Tags: Free Radic Biol Med Source Type: research

Melatonin alleviates heat stress-induced oxidative stress and apoptosis in human spermatozoa.
Abstract Oxidative stress generates a large amount of reactive oxygen species (ROS) and affects sperm quality via damaging sperm DNA and compromising the intracellular homeostasis in human spermatozoa. In assisted reproductive technology (ART), it is substantial to prevent spermatozoa from ROS attack. The pineal hormone melatonin has the natural antioxidant capacity and can scavenge ROS. To the best of our knowledge, however, there are presently no studies investigating if melatonin can protect human spermatozoa from heat-induced oxidative damage. Herein, we induced oxidative stress in human spermatozoa with heat ...
Source: Free Radical Biology and Medicine - January 19, 2021 Category: Biology Authors: Zhao F, Whiting S, Lambourne S, Aitken RJ, Sun YP Tags: Free Radic Biol Med Source Type: research

Anti-ageing effects of Ubiquinone and Ubiquinol in a senescence model of human dermal fibroblasts.
In conclusion, our results highlight the pivotal role of CoQ10 for skin vitality and strongly support the use of both forms as a beneficial and effective anti-ageing skin care treatment. PMID: 33482334 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 19, 2021 Category: Biology Authors: Marcheggiani F, Kordes S, Cirilli I, Orlando P, Silvestri S, Vogelsang A, Möller N, Blatt T, Weise JM, Damiani E, Tiano L Tags: Free Radic Biol Med Source Type: research

Nitric oxide and hydrogen sulfide: sibling rivalry in the family of epigenetic regulators.
Abstract Nitric oxide (NO) and hydrogen sulfide (H2S) were previously only known for their toxic properties. Now they are regarded as potent gaseous messenger molecules (gasotransmitters) that rapidly transverse cell membranes and transduce cellular signals through their chemical reactions and modifications to protein targets. Both are known to regulate numerous physiological functions including angiogenesis, vascular tone, and immune response, to name a few. NO and H2S often work synergistically and in competition to regulate each other's synthesis, target protein activity via posttranslational modifications (PTM...
Source: Free Radical Biology and Medicine - January 19, 2021 Category: Biology Authors: Kuschman HP, Palczewski MB, Thomas DD Tags: Free Radic Biol Med Source Type: research

Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury.
CONCLUSION: Lack of cardiomyocytes-specific MAO-B reduces infarct size suggesting that MAO-B activity contributes to acute reperfusion injury. PMID: 33476795 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 18, 2021 Category: Biology Authors: Heger J, Hirschhäuser C, Bornbaum J, Sydykov A, Dempfle A, Schneider A, Braun T, Schlüter KD, Schulz R Tags: Free Radic Biol Med Source Type: research

Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization.
SV Abstract Superoxide dismutase 3 (SOD3) is an extracellular protein with the capacity to convert superoxide into hydrogen peroxide, an important secondary messenger in redox regulation. To investigate the utility of zebrafish in functional studies of SOD3 and its relevance for redox regulation, we have characterized the zebrafish orthologues; Sod3a and Sod3b. Our analyses show that both recombinant Sod3a and Sod3b express SOD activity, however, only Sod3b is able to bind heparin. Furthermore, RT-PCR analyses reveal that sod3a and sod3b are expressed in zebrafish embryos and are present primarily in separate org...
Source: Free Radical Biology and Medicine - January 18, 2021 Category: Biology Authors: Matthiesen CL, Hu L, Torslev AS, Poulsen ET, Larsen UG, Kjaer-Sorensen K, Thomsen JS, Brüel A, Enghild JJ, Oxvig C, Petersen SV Tags: Free Radic Biol Med Source Type: research

Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages.
In conclusion, we proved that ADSCs exosomes alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating Nrf2/HO-1 expression. PMID: 33476797 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 18, 2021 Category: Biology Authors: Shen K, Jia Y, Wang X, Zhang J, Liu K, Wang J, Cai W, Li J, Li S, Zhao M, Wang Y, Hu D Tags: Free Radic Biol Med Source Type: research

Redox proteomics reveals an interdependence of redox modification and location of adhesome proteins in NGF-treated PC12 cells.
In conclusion, the suprastructural composition and function of adhesomes is redox-regulated by ROS. Of interest in this respect, isoform-selective pharmacological inhibition of NADPH-oxidases (Noxs) reduced the adhesomal location of the collagen-binding α1β1 integrin and the length of the outgrowing neurites, indicative of a role of Nox isoforms in the redox-regulation of adhesomes. Thus, our novel redox proteomics approach not only revealed redox-modifications and the potential redox-regulation of adhesomes and their constituents but it may also provide a tool to analyze the ROS-stimulated neurite repair of per...
Source: Free Radical Biology and Medicine - January 16, 2021 Category: Biology Authors: Meißner J, Rezaei M, Siepe I, Ackermann D, König S, Eble JA Tags: Free Radic Biol Med Source Type: research

Multiple 'omics'-analysis reveals the role of prostaglandin E2 in Hirschsprung's disease.
We examined colon tissues from three independent populations with a combined analysis of metabolomics, transcriptomics and proteomics to understand HSCR pathogenesis, according to which mouse model was used to examine prostaglandin E2 (PGE2) induced clinical presentation of HSCR. SH-SY5Y and SK-N-BE(2) cell lines were studied for PGE2 inhibited cell migration through EP2. Our integrated multiple 'omics'-analysis suggests that the levels of PGE2, the expression of the gene encoding PGE2 receptor (EP2), and PGE2 synthesis enzyme genes (PTGS1 and PTGES) increased in HSCR colon tissues, together with a decreased synthesis of P...
Source: Free Radical Biology and Medicine - January 16, 2021 Category: Biology Authors: Tang W, Chen M, Guo X, Zhou K, Wen Z, Liu F, Liu X, Mao X, He X, Hu W, Sun X, Tang J, Li H, White RA, Lv W, Wang P, Hang B, Sun R, Wang X, Xia Y Tags: Free Radic Biol Med Source Type: research

Redox sensor NPGPx restrains ZAP70 activity and modulates T cell homeostasis.
Abstract Emerging evidences implicate the contribution of ROS to T cell activation and signaling. The tyrosine kinase, ζ-chain-associated protein of 70 kDa (ZAP70), is essential for T cell development and activation. However, it remains elusive whether a direct redox regulation affects ZAP70 activity upon TCR stimulation. Here, we show that deficiency of non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), a redox sensor, results in T cell hyperproliferation and elevated cytokine productions. T cell-specific NPGPx-knockout mice reveal enhanced T-dependent humoral responses ...
Source: Free Radical Biology and Medicine - January 15, 2021 Category: Biology Authors: Su FY, Huang SC, Wei PC, Hsu PH, Li JP, Su LW, Hsieh YL, Hu CM, Hsu JL, Yang CY, Chung CY, Shew JY, Lan JL, Sytwu HK, Y-Hp Lee E, Lee WH Tags: Free Radic Biol Med Source Type: research

NQO1 mediates the anti-inflammatory effects of nootkatone in lipopolysaccharide-induced neuroinflammation by modulating the AMPK signaling pathway.
Abstract Neuroinflammation and oxidative stress play key roles in the progression of neurodegenerative diseases. Thus, the use of potent anti-inflammatory/antioxidant agents has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we investigated the anti-inflammatory and antioxidant effects of nootkatone (NKT), a sesquiterpenoid compound isolated from grapefruit, in in vitro and in vivo models of neuroinflammation. In lipopolysaccharide (LPS)-stimulated BV2 microglial cells, NKT inhibited the expression of iNOS, COX-2, and pro-inflammatory cytokines, and increas...
Source: Free Radical Biology and Medicine - January 15, 2021 Category: Biology Authors: Park JE, Park JS, Leem YH, Kim DY, Kim HS Tags: Free Radic Biol Med Source Type: research

Coenzyme Q homeostasis in aging: response to non-genetic interventions.
uch G Abstract Coenzyme Q (CoQ) is a key component for many essential metabolic and antioxidant activities in cells in mitochondria and cell membranes. Mitochondrial dysfunction is one of the hallmarks of aging and age-related diseases. Deprivation of CoQ during aging can be the cause or the consequence of this mitochondrial dysfunction. In any case, it seems clear that aging-associated CoQ deprivation accelerates mitochondrial dysfunction in these diseases. Non-genetic prolongevity interventions, including CoQ dietary supplementation, can increase CoQ levels in mitochondria and cell membranes improving mitochondr...
Source: Free Radical Biology and Medicine - January 14, 2021 Category: Biology Authors: López-Lluch G Tags: Free Radic Biol Med Source Type: research

β-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes low-grade inflammation and metabolic dysfunction.
β-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes low-grade inflammation and metabolic dysfunction. Free Radic Biol Med. 2021 Jan 13;: Authors: Wu L, Lu P, Guo X, Song K, Lyu Y, Bothwell J, Wu J, Hawkins O, Clarke SL, Lucas EA, Smith BJ, Chowanadisai W, Hartson SD, Ritchey JW, Wang W, Medeiros DM, Li S, Lin D Abstract Low-grade inflammation is a critical pathological factor contributing to the development of metabolic disorders. β-carotene oxygenase 2 (BCO2) was initially identified as an enzyme catalyzing carotenoids in the inner mitochondrial membrane. Mut...
Source: Free Radical Biology and Medicine - January 13, 2021 Category: Biology Authors: Wu L, Lu P, Guo X, Song K, Lyu Y, Bothwell J, Wu J, Hawkins O, Clarke SL, Lucas EA, Smith BJ, Chowanadisai W, Hartson SD, Ritchey JW, Wang W, Medeiros DM, Li S, Lin D Tags: Free Radic Biol Med Source Type: research

Antioxidant Function of Phytocannabinoids: Molecular Basis of Their Stability and Cytoprotective Properties under UV-irradiation.
Abstract In this contribution, a comprehensive study of the redox transformation, electronic structure, stability and photoprotective properties of phytocannabinoids is presented. The non-psychotropic cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and psychotropic tetrahydrocannabinol (THC) isomers and iso-THC were included in the study. The results show that under aqueous ambient conditions at pH 7.4, non-psychotropic cannabinoids are slight or moderate electron-donors and they are relatively stable, in the following order: CBD>CBG≥CBN>CBC. In contrast, psychotropic &Delt...
Source: Free Radical Biology and Medicine - January 13, 2021 Category: Biology Authors: Vacek J, Vostalova J, Papouskova B, Skarupova D, Kos M, Kabelac M, Storch J Tags: Free Radic Biol Med Source Type: research

Efficient iron utilization compensates for loss of extracellular matrix of ovarian cancer spheroids.
Abstract Metastasis is the major cause of death in women with advanced ovarian cancer. Epithelial ovarian cancer cells can dissociate directly from extracellular matrix (ECM) and form spheroids to spread through the peritoneal cavity. Loss of ECM hinders the survival of ECM-detached epithelial cells. It is still largely unknown how ovarian cancer spheroids maintain their viability after loss of ECM. We find that spheroids derived either from ovarian cancer ascites or cell lines are iron-replete. In accordance with iron-replete condition, proteins involved in iron uptake, transport and storage including divalent me...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Wang Q, Gu T, Ma L, Bu S, Zhou W, Mao G, Wang LL, Guo Y, Lai D Tags: Free Radic Biol Med Source Type: research

Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer.
Abstract The homeostatic oxygen sensing system (HOSS) optimizes systemic oxygen delivery. Specialized tissues utilize a conserved mitochondrial sensor, often involving NDUFS2 in complex I of the mitochondrial electron transport chain, as a site of pO2-responsive production of reactive oxygen species (ROS). These ROS are converted to a diffusible signaling molecule, hydrogen peroxide (H2O2), by superoxide dismutase (SOD2). H2O2 exits the mitochondria and regulates ion channels and enzymes, altering plasma membrane potential, intracellular Ca2+ and Ca2+-sensitization and controlling acute, adaptive, responses to hyp...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Wu D, Dasgupta A, Read AD, Bentley RET, Motamed M, Chen KH, Al-Qazazi R, Mewburn JD, Dunham-Snary KJ, Alizadeh E, Tian L, Archer SL Tags: Free Radic Biol Med Source Type: research

A role for 4-hydroxynonenal in premature placental senescence in Preeclampsia and Intrauterine Growth Restriction.
In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived aldehyde present in preeclamptic placentas, may contribute to premature senescence in placenta-related complications. Placentas from PE-affected women, exhibited several senescence patterns, such as an increased expression of phosphorylated (serine-139) histone γ-H2AX, a sensitive marker of double-stranded DNA breaks, the presence of lipofuscin granules, and an accumulation of high molecular weight cross-linked and ubiquitinated proteins. PE placentas showed an accumulation of acetylated proteins consistent with the presenc...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Tasta O, Swiader A, Grazide MH, Rouahi M, Parant O, Vayssière C, Bujold E, Salvayre R, Guerby P, Negre-Salvayre A Tags: Free Radic Biol Med Source Type: research

The epigenetic and morphogenetic effects of molecular oxygen and its derived reactive species in development.
Abstract The development of multicellular organisms involves the unpacking of a complex genetic program. Extensive characterization of discrete developmental steps has revealed the genetic program is controlled by an epigenetic state. Shifting the epigenome is a group of epigenetic enzymes that modify DNA and proteins to regulate cell type specific gene expression. While the role of these modifications in development has been established, the input(s) responsible for electing changes in the epigenetic state remains unknown. Development is also associated dynamic changes in cellular metabolism, redox, free radical ...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Hitchler MJ, Domann FE Tags: Free Radic Biol Med Source Type: research

Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease.
Abstract Chronic kidney disease (CKD) leads to deep changes in lipid metabolism and obvious dyslipidemia. The dysregulation of lipid metabolism in turn results in CKD progression and the complications of cardiovascular diseases. To obtain a profound insight into the associated dyslipidemia in CKD, we performed lipidomic analysis to measure lipid metabolites in the serum from a rat 5/6 nephrectomy (5/6 Nx) model of CKD as well as in the serum from CKD patients. HK-2 cells were also used to examine oxidative stress-induced sphingolipid changes. Totally 182 lipid species were identified in 5/6 Nx rats. We found glyce...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Gui T, Li Y, Zhang S, Alecu I, Chen Q, Zhao Y, Hornemann T, Kullak-Ublick GA, Gai Z Tags: Free Radic Biol Med Source Type: research

Coenzyme Q redox, signalling and longevity.
Abstract Mitochondria are the powerhouses of the cell. They produce a significant amount of the energy we need to grow, survive and reproduce. The same system that generates energy in the form of ATP also produces Reactive Oxygen Species (ROS). Mitochondrial Reactive Oxygen Species (mtROS) were considered for many years toxic by-products of metabolism, responsible for ageing and many degenerative diseases. Today, we know that mtROS are essential redox messengers required to determine cell fate and maintain cellular homeostasis. Most mtROS are produced by respiratory complex I (CI) and complex III (CIII). How and w...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Scialo F, Sanz A Tags: Free Radic Biol Med Source Type: research

Expanding the link between circadian rhythms and redox metabolism of epigenetic control.
Abstract Circadian rhythms play a central role in physiological and metabolic processes. This is mostly achieved through rhythmic regulation of myriad genes via dynamic epigenome changes. Accumulating evidence indicates that oxidative stress and redox balance are under circadian control and feedback on the clock system. Circadian perturbations induce oxidative stress accumulation and disturb redox balance. Along with these changes, epigenomic landscape changes are a remarkable hallmark of clock disruption. This review aims to summarize evidence supporting the link between the circadian clock and redox metabolism, ...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Sato T, Greco CM Tags: Free Radic Biol Med Source Type: research

Downregulation of CD151 induces oxidative stress and apoptosis in trophoblast cells via inhibiting ERK/Nrf2 signaling pathway in preeclampsia.
Abstract Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we ...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Wang Z, Cai B, Cao C, Lv H, Dai Y, Zheng M, Zhao G, Peng Y, Gou W, Wang J, Liu D, Hu Y Tags: Free Radic Biol Med Source Type: research

Secondary coenzyme q deficiency in neurological disorders.
Abstract Coenzyme Q (CoQ) is a ubiquitous lipid serving essential cellular functions. It is the only component of the mitochondrial respiratory chain that can be exogenously absorbed. Here, we provide an overview of current knowledge, controversies, and open questions about CoQ intracellular and tissue distribution, in particular in brain and skeletal muscle. We discuss human neurological diseases and mouse models associated with secondary CoQ deficiency in these tissues and highlight pharmacokinetic and anatomical challenges in exogenous CoQ biodistribution, recent improvements in CoQ formulations and imaging, as...
Source: Free Radical Biology and Medicine - January 12, 2021 Category: Biology Authors: Gueguen N, Baris O, Lenaers G, Reynier P, Spinazzi M Tags: Free Radic Biol Med Source Type: research

Regulation of the epigenetic landscape by immune cell oxidants.
Abstract Excessive production of microbicidal oxidants by neutrophils can damage host tissue. The short-term response of cells to oxidative stress is well understood, but the mechanisms behind long-term consequences require further clarification. Epigenetic pathways mediate cellular adaptation, and are therefore a potential target of oxidative stress. Indeed, there is evidence that many proteins and metabolites involved in epigenetic pathways are redox sensitive. In this review we provide an overview of the epigenetic landscape and discuss the potential for redox regulation. Using this information, we highlight sp...
Source: Free Radical Biology and Medicine - January 11, 2021 Category: Biology Authors: Das AB, Seddon AR, O'Connor KM, Hampton MB Tags: Free Radic Biol Med Source Type: research

Transcription of MRPL12 regulated by Nrf2 contributes to the mitochondrial dysfunction in diabetic kidney disease.
Abstract Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increasing evidences suggested that DKD correlates more closely to mitochondrial dysfunction than to hyperglycemia. Our previous study has reported that mitochondrial ribosomal protein L7/L12 (MRPL12) could positively control the mitochondrial oxidative phosphorylation (OXPHOS) and mtDNA copy number. The present study further investigated the role of MRPL12 in mitochondrial dysfunction of DKD. Using a mass spectrometry-based proteomics and immunohistochemistry, we found that MRPL12 underw...
Source: Free Radical Biology and Medicine - January 11, 2021 Category: Biology Authors: Gu X, Liu Y, Wang N, Zhen J, Zhang B, Hou S, Cui Z, Wan Q, Feng H Tags: Free Radic Biol Med Source Type: research

Cysteamine Assay for the Evaluation of Bioactive Electrophiles.
In this study, we developed a simple cysteamine assay which can be used to study the reactivity of electrophilic compounds towards primary amine and thiol groups in an aqueous environment. The detection principle is based on the electrochemical, photometrical and mass spectrometric analyses of cysteamine (2-aminoethanethiol) as the molecular probe. This technique is useful for studying the reaction kinetics of electrophiles with thiol (SH) and amino (NH2) groups. The decrease in analytical responses of cysteamine was monitored to evaluate the reactivity of three electrophilic activators of the Nrf2 pathway, which mediates ...
Source: Free Radical Biology and Medicine - January 8, 2021 Category: Biology Authors: Novák D, Vrba J, Zatloukalová M, Roubalová L, Stolarczyk K, Dorčák V, Vacek J Tags: Free Radic Biol Med Source Type: research

Neuroprotective effects of Myricetin on Epoxiconazole-induced toxicity in F98 cells.
This study indicates that pre-treatment of F98 cells with Myricetin during two hours before Epoxiconazole exposure significantly increased the survival of cells, restored DNA synthesis of the S phase, abrogated the ROS generation, regulated the activities of Catalase (CAT) and Superoxide Dismutase (SOD), and reduced the MDA level. The loss of mitochondrial membrane potential, DNA fragmentation, cytoskeleton disruption, chromatin condensation, Phosphatidylserine externalization, and Caspases activation were also reduced by Myricetin. Together, these findings indicate that Myricetin is a powerful natural product able to prot...
Source: Free Radical Biology and Medicine - January 8, 2021 Category: Biology Authors: Hamdi H, Abid-Essefi S, Eyer J Tags: Free Radic Biol Med Source Type: research

The Metabolic-Epigenetic Nexus in Type 2 Diabetes Mellitus.
Abstract The prevalence of type 2 diabetes mellitus (T2DM) continues to rise globally. Yet the aetiology and pathophysiology of this noncommunicable, polygenic disease, is poorly understood. Lifestyle factors, such as poor dietary intake, lack of exercise, and abnormal glycaemia, are purported to play a role in disease onset and progression, and these environmental factors may disrupt specific epigenetic mechanisms, leading to a reprogramming of gene transcription. The hyperglycaemic cell per se, alters epigenetics through chemical modifications to DNA and histones via metabolic intermediates such as succinate, &a...
Source: Free Radical Biology and Medicine - January 8, 2021 Category: Biology Authors: Davison GW, Irwin RE, Walsh CP Tags: Free Radic Biol Med Source Type: research

Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress.
Abstract Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma with age (HCC). Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the disease progression from NASH to fibrosis. Because necroptosis is a major sour...
Source: Free Radical Biology and Medicine - January 8, 2021 Category: Biology Authors: Mohammed S, Nicklas EH, Thadathil N, Selvarani R, Royce GH, Kinter M, Richardson A, Deepa SS Tags: Free Radic Biol Med Source Type: research

Therapeutic effects of non-saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease.
Abstract Biological aging provokes morbidity and several functional declines, causing older adults more susceptible to a variety of diseases than younger adults. In particular, aging is a major risk factor contributing to non-communicable diseases, such as neurodegenerative disorders. Alzheimer's disease (AD) is an aging-related neurodegenerative disease that is characterized by cognitive deficits and the formation of amyloid plaques formed by the accumulation of amyloid-β (Aβ) peptides. Non-saponin fraction with rich polysaccharide (NFP) from red ginseng, the largest fraction of the components of red gi...
Source: Free Radical Biology and Medicine - January 7, 2021 Category: Biology Authors: Shin SJ, Nam Y, Park YH, Kim MJ, Lee E, Jeon SG, Bae BS, Seo J, Shim SL, Kim JS, Han CK, Kim S, Lee YY, Moon M Tags: Free Radic Biol Med Source Type: research

The use of glutathione to reduce oxidative stress status and its potential for modifying the extracellular matrix organization in cleft lip.
CONCLUSIONS: The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future. PMID: 33422675 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 7, 2021 Category: Biology Authors: Li R, Huang C, Hin Ho JC, Tim Leung CC, Chong Kong RY, Li Y, Liang X, Po Lai K, Fai Tse WK Tags: Free Radic Biol Med Source Type: research

Cell therapy for the treatment of heart disease: renovation work on the broken heart is still in progress.
Abstract Cardiovascular disease (CVD) continues to be the number one killer in the aging population. Heart failure (HF) is also an important cause of morbidity and mortality in patients with congenital heart disease (CHD). Novel therapeutic approaches that could restore stable heart function are much needed in both paediatric and adult patients. Regenerative medicine holds promises to provide definitive solutions for correction of congenital and acquired cardiac defects. In this review article, we recap some important aspects of cardiovascular cell therapy. First, we report quantifiable data regarding the scientif...
Source: Free Radical Biology and Medicine - January 6, 2021 Category: Biology Authors: Madeddu P Tags: Free Radic Biol Med Source Type: research

Superoxide produced by mitochondrial site IQ inactivates cardiac succinate dehydrogenase and induces hepatic steatosis in Sod2 knockout mice.
Abstract Superoxide produced by mitochondria has been implicated in numerous physiologies and pathologies. Eleven different mitochondrial sites that can produce superoxide and/or hydrogen peroxide (O2.-/H2O2) have been identified in vitro, but little is known about their contributions in vivo. We introduce novel variants of S1QELs and S3QELs (small molecules that suppress O2.-/H2O2 production specifically from mitochondrial sites IQ and IIIQo, respectively, without compromising bioenergetics), that are suitable for use in vivo. When administered by intraperitoneal injection, they achieve total tissue concentration...
Source: Free Radical Biology and Medicine - January 6, 2021 Category: Biology Authors: Wong HS, Mezera V, Dighe P, Melov S, Gerencser AA, Sweis RF, Pliushchev M, Wang Z, Esbenshade T, McKibben B, Riedmaier S, Brand MD Tags: Free Radic Biol Med Source Type: research

One-Electron Reduction Triggered Nitric Oxide Release for Ischemia-Reperfusion Protection.
Abstract Nitric oxide donors (NODs) are indispensable in biological research and disease treatment. NODs had been utilized to treat cardiovascular diseases in clinic and many others are under trial. Thiols are typically required for these donors to release NO. Yet, their mechanism is complex and often lead to resistance. Herein, we reported that N-nitrosated electron-deficient dyes are capable of NO release with one-electron reduction. A fluorophore is generated simultaneously, whose fluorescence is harnessed to monitor the profile of NO release. Through electrochemical and spectral studies, NOD f3 was found to ex...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Xu X, Sun M, Luo X, Zhang Z, Su L, Cui L, Zhu Z, Lu X, Wang R, Han F, Qian X, Yang Y Tags: Free Radic Biol Med Source Type: research

Abnormal nitration and S-sulfhydration modification of Sp1-CSE-H2S pathway trap the progress of hyperhomocysteinemia into a vicious cycle.
This study focused on the post-translational modification of Sp1/CSE and revealed four major findings: (1) Homocysteine-accumulation augmented CSE's nitration, inhibited its bio-activity, thus caused H2S deficiency. (2) H2S deficiency inhibited the S-sulfhydration of Sp1, down-regulated CSE and decreased H2S further, which in turn weakened CSE's own S-sulfhydration. (3) CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310, among which the S-sulfhydration of Cys172 and Cys310 didn't affect its enzymatic activity, while the S-sulfhydration of Cys84, Cys109, Cys229, Cys252 and Cys307 was necessar...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Luo C, Ji D, Li Y, Cao Y, Zhang S, Yan W, Xue K, Chai J, Wu Y, Liu H, Wang W Tags: Free Radic Biol Med Source Type: research

Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy.
In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectivel...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: White TL, Deshpande N, Kumar V, Gauthier AG, Jurkunas UV Tags: Free Radic Biol Med Source Type: research

Endothelial Nox4 dysfunction aggravates atherosclerosis by inducing endoplasmic reticulum stress and soluble epoxide hydrolase.
CONCLUSIONS: Endothelial Nox4 dysfunction upregulated sEH to enhance inflammation, probably by its induction of ER stress. Inhibition of ER stress or sEH is beneficial to alleviate atherosclerosis caused by endothelial Nox4 dysfunction. PMID: 33418110 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Yu W, Li S, Wu H, Hu P, Chen L, Zeng C, Tong X Tags: Free Radic Biol Med Source Type: research

Asymmetrical Arginine Dimethylation of Histone H4 by 8-oxoG/OGG1/PRMT1 is Essential for Oxidative Stress-induced Transcription Activation.
Abstract It has been established that 8-oxoguanine DNA glycosylase 1 (OGG1) is the main enzyme removing oxidized guanine under oxidative stress. However, increasing evidence has shown that OGG1 is not only a base excision repair protein but also a new transcriptional coactivator involved in oxidative stress-induced gene expression. Its downstream target genes and the underlying regulatory mechanisms still need to be discerned. Here, it was discovered that c-Myc is a downstream target of OGG1 under oxidative stress and that H4R3me2a is involved in this transcriptional regulation. The increased level of H4R3me2a ind...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Wang W, Ma Y, Huang M, Liang W, Zhao X, Li Q, Wang S, Hu Z, He L, Gao T, Chen J, Pan F, Guo Z Tags: Free Radic Biol Med Source Type: research

Mitigation of radiation-induced pulmonary fibrosis by small-molecule dye IR-780.
Abstract Radiation-induced pulmonary fibrosis (RIPF) is a common complication during thoracic radiotherapy, but there are few effective treatments. Here, we identify IR-780, a mitochondria-targeted near-infrared (NIR) dye, can selectively accumulate in the irradiated lung tissues. Besides, IR-780 significantly alleviates radiation-induced acute lung injury and fibrosis. Furthermore, our results show that IR-780 prevents the differentiation of fibroblasts and the release of pro-fibrotic factors from alveolar macrophages induced by radiation. Besides, IR-780 downregulates the expression of glycolysis-associated gene...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Luo M, Chen L, Zheng J, Wang Q, Huang Y, Liao F, Jiang Z, Zhang C, Shen G, Wu J, Wang Y, Wang Y, Leng Y, Han S, Zhang A, Wang Z, Shi C Tags: Free Radic Biol Med Source Type: research

Small Extracellular Vesicle-mediated Hsp70 Intercellular Delivery Enhances Breast Cancer Adriamycin Resistance.
Abstract Adriamycin (ADR) resistance poses a significant challenge for successfully treating breast cancer (BCa). The mechanism underlying intrinsically acquisition of the resistance remains to be fully elucidated. Here, we describe that small extracellular vesicles (sEVs) mediated Hsp70 transfer is implicated in ADR resistance. The resistant cells derived sEVs were incubated with sensitive cells, thereby transmitting the resistant phenotype to the recipient cells. The internalization of the sEVs in the recipient cells and sEV-mediated Hsp70 transfer into mitochondria were examined by confocal microscope and trans...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Hu W, Xu Z, Zhu S, Sun W, Wang X, Tan C, Zhang Y, Zhang G, Xu Y, Tang J Tags: Free Radic Biol Med Source Type: research

Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis.
In this study, we used LC-MS/MS to measure the archetypical tobacco-specific carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), three biomarkers of oxidative stress (8-oxo-7,8-dihydroguanine, 8-oxoGua; 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodGuo; 8-oxo-7,8-dihydroguanosine, 8-oxoGuo) and two biomarkers of alkylating stress (N7-methylguanine, N7-MeGua and N3-methyladenine, N3-MeAde), in the urine of smoking and non-smoking COPD patients and healthy controls. Our results showed that not only was oxidative stress significantly eleva...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: Shih YM, Chang YJ, Cooke MS, Pan CH, Hu CH, Chao MR, Hu CW Tags: Free Radic Biol Med Source Type: research

Overexpression of Glucose 6 Phosphate Dehydrogenase preserves mouse pancreatic beta cells function until late in life.
e;a J Abstract NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6-phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide. This enzymopathy provides protection against malaria but sensitizes cells to oxidative stressors. Oxidative stress has been involved in the pathogenesis of the diabetic complications and several studies have provided evidences of a link between G6PD deficiency and type 2 diabetes (T2D). We hypothesized that a moderate overexpression of G6PD (G6PD-Tg) ...
Source: Free Radical Biology and Medicine - January 5, 2021 Category: Biology Authors: la Rosa A, Gomez-Cabrera MC, A V, Gonzalez-Navarro H, Sanchez-Andres JV, Viña J Tags: Free Radic Biol Med Source Type: research

Commentary on "Azocompounds as generators of defined radical species: Contributions and challenges for free radical research" by L ópez-Alarcón et al. [Free Radic. Biol. Med. 160 (2020) 78-91].
Commentary on "Azocompounds as generators of defined radical species: Contributions and challenges for free radical research" by López-Alarcón et al. [Free Radic. Biol. Med. 160 (2020) 78-91]. Free Radic Biol Med. 2021 Jan 04;: Authors: Niki E PMID: 33412271 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 4, 2021 Category: Biology Authors: Niki E Tags: Free Radic Biol Med Source Type: research