Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1
Publication date: Available online 19 April 2019Source: Redox BiologyAuthor(s): Liya Chen, Anna L. Lang, Gavin D. Poff, Wen-Xing Ding, Juliane I. BeierAbstractVinyl chloride (VC), an abundant environmental contaminant causes steatohepatitis at high levels, but is considered safe at lower (i.e., sub-OSHA) levels. However, we have previously shown that even lower VC levels exacerbate experimental nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD). Mitochondrial oxidative injury and subsequent metabolic dysfunction appeared to play key roles in mediating this interaction. Mitochondrial aldehyde dehydrogena...
Source: Redox Biology - April 19, 2019 Category: Biology Source Type: research

Measuring intracellular concentration of hydrogen peroxide with the use of genetically encoded H2O2 biosensor HyPer
In this study, we propose a method for quantification of average hydrogen peroxide concentration within a living cell that is based on the use of genetically encoded H2O2 biosensor HyPer. The method utilizes flow cytometric measurements of HyPer fluorescence in H2O2-exposed cells to analyze the biosensor oxidation kinetics. Fitting the experimental curves with kinetic equations allows determining the rate constants of HyPer oxidation/reduction which are used further for the calculation of peroxide concentrations in the cells of interest both in the presence and absence of external H2O2. Applying this method to K562 cells...
Source: Redox Biology - April 17, 2019 Category: Biology Source Type: research

Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway
Publication date: Available online 17 April 2019Source: Redox BiologyAuthor(s): Jie Shi, Shibo Sun, Yan Liao, Jing Tang, Xiaoping Xu, Biyan Qin, Caolitao Qin, Lishan Peng, Mengshi Luo, Lan Bai, Fang XieAbstractIntestinal epithelial cell (IEC) cycle arrest has recently been found to be involved in the pathogenesis of Crohn's disease (CD). However, the mechanism underlying the regulation of this form of cell cycle arrest, remains unclear. Here, we investigated the roles that advanced oxidation protein products (AOPPs) may play in regulating IEC cycle arrest. Plasma AOPPs levels and IEC cycle distributions were evaluated in 1...
Source: Redox Biology - April 17, 2019 Category: Biology Source Type: research

Peroxiredoxin-mediated disulfide bond formation is required for nucleocytoplasmic translocation and secretion of HMGB1 in response to inflammatory stimuli
Publication date: Available online 15 April 2019Source: Redox BiologyAuthor(s): Man Sup Kwak, Hee Sue Kim, Khulan Lkhamsuren, Young Hun Kim, Myeong Gil Han, Jae Min Shin, In Ho Park, Woo Joong Rhee, Se Kyoung Lee, Sue Goo Rhee, Jeon-Soo ShinAbstractThe nuclear protein HMGB1 (high mobility group box 1) is secreted by monocytes-macrophages in response to inflammatory stimuli and serves as a danger-associated molecular pattern. Acetylation and phosphorylation of HMGB1 are implicated in the regulation of its nucleocytoplasmic translocation for secretion, although inflammatory stimuli are known to induce H2O2 production. Here w...
Source: Redox Biology - April 16, 2019 Category: Biology Source Type: research

Gender- and age-dependencies of oxidative stress, as detected based on the steady state concentrations of different biomarkers in the MARK-AGE study
In conclusion, it appears that all the biomarkers assessed here reflect different types of OS and that MDA and GSH reflect the same type of OS.Graphical abstract (Source: Redox Biology)
Source: Redox Biology - April 16, 2019 Category: Biology Source Type: research

Voltage gated proton channels modulate mitochondrial reactive oxygen species production by complex I in renal medullary thick ascending limb
Publication date: Available online 16 April 2019Source: Redox BiologyAuthor(s): Bansari Patel, Nadezhda N. Zheleznova, Sarah C. Ray, Jingping Sun, Allen W. Cowley, Paul M. O'ConnorAbstractHv1 is a voltage-gated proton channel highly expressed in immune cells where, it acts to maintain NAD(P)H oxidase activity during the respiratory burst. We have recently reported that Hv1 is expressed in cells of the medullary thick ascending limb (mTAL) of the kidney and is critical to augment reactive oxygen species (ROS) production by this segment. While Hv1 is associated with NOX2 mediated ROS production in immune cells, the source of...
Source: Redox Biology - April 16, 2019 Category: Biology Source Type: research

Limitations to adaptive homeostasis in an hyperoxia-induced model of accelerated ageing
Publication date: Available online 14 April 2019Source: Redox BiologyAuthor(s): Laura C.D. Pomatto, Patrick Y. Sun, Kelsi Yu, Sandhyarani Gullapalli, Conscience P. Bwiza, Christina Sisliyan, Sarah Wong, Hongqiao Zhang, Henry Jay Forman, Peter L. Oliver, Kay E. Davies, Kelvin J.A. DaviesAbstractThe Nrf2 signal transduction pathway plays a major role in adaptive responses to oxidative stress and in maintaining adaptive homeostasis, yet Nrf2 signaling undergoes a significant age-dependent decline that is still poorly understood. We used mouse embryonic fibroblasts (MEFs) cultured under hyperoxic conditions of 40% O2, as a mod...
Source: Redox Biology - April 14, 2019 Category: Biology Source Type: research

Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis
Publication date: Available online 13 April 2019Source: Redox BiologyAuthor(s): Teagan S. Hoskin, Jennifer M. Crowther, Jeanette Cheung, Michael J. Epton, Peter D. Sly, Peter A. Elder, Renwick C.J. Dobson, Anthony J. Kettle, Nina DickerhofAbstractCalprotectin, the major neutrophil protein, is a critical alarmin that modulates inflammation and plays a role in host immunity by strongly binding trace metals essential for bacterial growth. It has two cysteine residues favourably positioned to act as a redox switch. Whether their oxidation occurs in vivo and affects the function of calprotectin has received little attention. He...
Source: Redox Biology - April 13, 2019 Category: Biology Source Type: research

Inhibition of Brd4 alleviates renal ischemia/reperfusion injury-induced apoptosis and endoplasmic reticulum stress by blocking FoxO4-mediated oxidative stress
In conclusion, our results proved that Brd4 inhibition blocked renal apoptotic and ERS protein expression by preventing FoxO4-dependent ROS generation through the PI3K/AKT pathway, indicating that Brd4 could be a potential therapeutic target for renal I/R injury.Graphical abstract (Source: Redox Biology)
Source: Redox Biology - April 13, 2019 Category: Biology Source Type: research

Hyperhomocysteinemia-induced death of retinal ganglion cells: The role of Müller glial cells and NRF2
Publication date: Available online 11 April 2019Source: Redox BiologyAuthor(s): Soumya Navneet, Jing Zhao, Jing Wang, Barbara Mysona, Shannon Barwick, Navneet Ammal Kaidery, Alan Saul, Ismail Kaddour-Djebbar, Wendy B. Bollag, Bobby Thomas, Kathryn E. Bollinger, Sylvia B. SmithAbstractHyperhomocysteinemia (Hhcy), or increased levels of the excitatory amino acid homocysteine (Hcy), is implicated in glaucoma, a disease characterized by increased oxidative stress and loss of retinal ganglion cells (RGCs). Whether Hhcy is causative or merely a biomarker for RGC loss in glaucoma is unknown. Here we analyzed the role of NRF2, a m...
Source: Redox Biology - April 13, 2019 Category: Biology Source Type: research

Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells
Publication date: Available online 9 April 2019Source: Redox BiologyAuthor(s): Bowen Xie, Lu Zhang, Wenfeng Hu, Ming Fan, Nian Jiang, Yumei Duan, Di Jing, Wenwu Xiao, Ruben C. Fragoso, Kit S. Lam, Lun-Quan Sun, Jian Jian LiAbstractRadiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative ...
Source: Redox Biology - April 10, 2019 Category: Biology Source Type: research

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice
Publication date: Available online 10 April 2019Source: Redox BiologyAuthor(s): Stefano Tarantini, Marta Noa Valcarcel-Ares, Peter Toth, Andriy Yabluchanskiy, Zsuzsanna Tucsek, Tamas Kiss, Peter Hertelendy, Michael Kinter, Praveen Ballabh, Zoltán Süle, Eszter Farkas, Joseph A. Baur, David A. Sinclair, Anna Csiszar, Zoltan UngvariAbstractAdjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cogn...
Source: Redox Biology - April 10, 2019 Category: Biology Source Type: research

A Golgi-associated redox switch regulates catalytic activation and cooperative functioning of ST6Gal-I with B4GalT-I
Publication date: Available online 4 April 2019Source: Redox BiologyAuthor(s): Antti Hassinen, Fawzi Khoder-Agha, Elham Khosrowabadi, Daniela Mennerich, Deborah Harrus, Maxcence Noel, Elitsa Y. Dimova, Tuomo Glumoff, Anne Harduin-Lepers, Thomas Kietzmann, Sakari KellokumpuAbstractGlycosylation, a common modification of cellular proteins and lipids, is often altered in diseases and pathophysiological states such as hypoxia, yet the underlying molecular causes remain poorly understood. By utilizing lectin microarray glycan profiling, Golgi pH and redox screens, we show here that hypoxia inhibits terminal sialylation of N- an...
Source: Redox Biology - April 5, 2019 Category: Biology Source Type: research

S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer
Publication date: Available online 5 April 2019Source: Redox BiologyAuthor(s): Adriana Karla Cardoso Amorim Reis, Arnold Stern, Hugo Pequeno MonteiroAbstractNitric Oxide (NO) and Hydrogen Sulfide (H2S) are components of an “interactome”, which is defined as a redox system involving the interactions of RSS, RNS and ROS. Chemical interaction by these species is common and is characterized by one and two electron oxidation, nitrosylation, nitration and sulfuration/polysulfidation reactions. NO and H2S are gases that penetrate cell membranes, are synthesized by specific enzymes, are ubiquitous, regulate protein act...
Source: Redox Biology - April 5, 2019 Category: Biology Source Type: research

Adaptations to high-intensity interval training in skeletal muscle require NADPH oxidase 2
ConclusionThis study suggests that HIIT exercise increases NOX2 activity in skeletal muscle and shows that NOX2 activity is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.Graphical abstract (Source: Redox Biology)
Source: Redox Biology - April 4, 2019 Category: Biology Source Type: research

FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice
Publication date: Available online 3 April 2019Source: Redox BiologyAuthor(s): Dae Hyun Kim, Bonggi Lee, Jaewon Lee, Mi Eun Kim, Jun Sik Lee, Jae Heun Chung, Byung Pal Yu, H. Henry Dong, Hae Young ChungAbstractFoxO has been proposed to play a role in the promotion of insulin resistance, and inflammation. FoxO is a pro-inflammatory transcription factor that is a key mediator of generation of inflammatory cytokines such as IL-1β in the liver. However, the detailed association of FoxO6 with insulin resistance and age-related inflammation has not been fully documented. Here, we showed that FoxO6 was elevated in the livers...
Source: Redox Biology - April 4, 2019 Category: Biology Source Type: research

Cholesterol crystals promote endothelial cell and monocyte interactions via H2O2-mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression
Publication date: Available online 3 April 2019Source: Redox BiologyAuthor(s): Prahalathan Pichavaram, Arul M. Mani, Nikhlesh K. Singh, Gadiparthi N. RaoAbstractIn the present study, we show that cholesterol crystals induce NFκB activation, and ICAM1 and VCAM1 expression via xanthine oxidase-mediated H2O2 production and PP2A inhibition in influencing endothelial cell and monocyte interactions and all these adverse effects of cholesterol crystals could be attenuated by proresolving lipid mediator RvD1. In addition, feeding mice with cholesterol rich diet (CRD) increased xanthine oxidase expression, its activity and H2...
Source: Redox Biology - April 4, 2019 Category: Biology Source Type: research

Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide
In conclusion, EpoL, a new variant of Epo without hematopoietic activity, is of potential interest for the treatment of diseases related to oxidative stress in the CNS such as Alzheimer disease.Graphical abstract (Source: Redox Biology)
Source: Redox Biology - April 3, 2019 Category: Biology Source Type: research

Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidative stress
Publication date: Available online 2 April 2019Source: Redox BiologyAuthor(s): Debapriya Chakraborty, Vanessa Felzen, Christof Hiebel, Elisabeth Stürner, Natarajan Perumal, Caroline Manicam, Elisabeth Sehn, Franz Grus, Uwe Wolfrum, Christian BehlAbstractOxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress in...
Source: Redox Biology - April 3, 2019 Category: Biology Source Type: research

TLR4 participates in sympathetic hyperactivity Post-MI in the PVN by regulating NF-κB pathway and ROS production
Publication date: Available online 2 April 2019Source: Redox BiologyAuthor(s): Yu Wang, Hesheng Hu, Jie Yin, Yugen Shi, Jiayu Tan, Lu Zheng, Cailing Wang, Xiaolu Li, Mei Xue, Ju Liu, Ye Wang, Yan Li, Xinran Li, Fuhong Liu, Qiang Liu, Suhua YanAbstractSympathetic nerve hyperactivity is a primary reason for fatal ventricular arrhythmias (VAs) following myocardial infarction (MI). Pro-inflammatory cytokines produced in the paraventricular nucleus (PVN) post-MI are associated with sympathetic overexcitation; however, the precise mechanism needs further investigation. Our aim was to explore the mechanism of toll-like receptor 4...
Source: Redox Biology - April 3, 2019 Category: Biology Source Type: research

The early response of αB-crystallin to a single bout of aerobic exercise in mouse skeletal muscles depends upon fiber oxidative features
This study provides novel information on the molecular pathway underlying the HSPB5 physiological function in skeletal muscle, confirming the contribution of the pro-oxidant environment in HSPB5 activation and interaction with substrate/client myofibrillar proteins, offering new insights for the study of myofibrillar myopathies and cardiomyopathies. (Source: Redox Biology)
Source: Redox Biology - April 3, 2019 Category: Biology Source Type: research

Knockout of dihydrofolate reductase in mice induces hypertension and abdominal aortic aneurysm via mitochondrial dysfunction
Publication date: Available online 29 March 2019Source: Redox BiologyAuthor(s): Qiang Li, Ji Youn Youn, Kin Lung Siu, Priya Murugesan, Yixuan Zhang, Hua CaiAbstractHypertension and abdominal aortic aneurysm (AAA) are severe cardiovascular diseases with incompletely defined molecular mechanisms. In the current study we generated dihydrofolate reductase (DHFR) knockout mice for the first time to examine its potential contribution to the development of hypertension and AAA, as well as the underlying molecular mechanisms. Whereas the homozygote knockout mice were embryonically lethal, the heterozygote knockout mice had global ...
Source: Redox Biology - March 30, 2019 Category: Biology Source Type: research

Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
We report here the characterization of the first generated endogenous redox-inactive thioredoxin in an animal model, the TRX-1 in the nematode Caenorhabditis elegans. We find that TRX-1 dually regulates the formation of an endurance larval stage (dauer) by interacting with the insulin pathway in a redox-independent manner and the cGMP pathway in a redox-dependent manner. Moreover, the requirement of TRX-1 for the extended longevity of worms with compromised insulin signalling or under calorie restriction relies on TRX-1 redox activity. In contrast, the nuclear translocation of the SKN-1 transcription factor and increased L...
Source: Redox Biology - March 30, 2019 Category: Biology Source Type: research

15-Keto prostaglandin E2 suppresses STAT3 signaling and inhibits breast cancer cell growth and progression
In this study, we observed that 15-keto PGE2 suppressed the phosphorylation, dimerization and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) that is constitutively activated in human mammary epithelial cells transfected with H-ras (MCF10A-ras). 15-Keto PGE2 inhibited the migration and clonogenicity of MCF10A-ras cells. In addition, subcutaneous injection of 15-keto PGE2 attenuated xenograft tumor growth and phosphorylation of STAT3 induced by breast cancer MDA-MB-231 cells. However, a non-electrophilic analogue, 13,14-dihydro-15-keto PGE2 failed to inhibit STAT3 signaling and was unab...
Source: Redox Biology - March 30, 2019 Category: Biology Source Type: research

Using resonance synchronous spectroscopy to characterize the reactivity and electrophilicity of biologically relevant sulfane sulfur
We report the discovery that reactive sulfane sulfur such as polysulfides and persulfides could be detected by using resonance synchronous spectroscopy (RS2). With RS2, we showed that inorganic polysulfides at low concentrations were unstable with a half-life about 1 min under physiological conditions due to reacting with glutathione. The protonated form of glutathione persulfide (GSSH) was electrophilic and had RS2 signal. GSS− was nucleophilic, prone to oxidation, but had no RS2 signal. Using this phenomenon, pKa of GSSH was determined as 6.9. GSSH/GSS− was 50-fold more reactive than H2S/HS− towards H...
Source: Redox Biology - March 27, 2019 Category: Biology Source Type: research

SELENON (SEPN1) protects skeletal muscle from saturated fatty acid-induced ER stress and insulin resistance
Publication date: Available online 23 March 2019Source: Redox BiologyAuthor(s): Ersilia Varone, Diego Pozzer, Simona Di Modica, Alexander Chernorudskiy, Leonardo Nogara, Martina Baraldo, Mario Cinquanta, Stefano Fumagalli, Rocio Nur Villar-Quiles, Maria-Grazia De Simoni, Bert Blaauw, Ana Ferreiro, Ester ZitoAbstractSelenoprotein N (SELENON) is an endoplasmic reticulum (ER) protein whose loss of function leads to congenital myopathies associated with insulin resistance (SEPN1-related myopathies). The exact cause of the insulin resistance in patients with SELENON loss of function is not known. Skeletal muscle is the main con...
Source: Redox Biology - March 24, 2019 Category: Biology Source Type: research

Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats
Publication date: Available online 21 March 2019Source: Redox BiologyAuthor(s): Tsung-Ming Lee, Horng-Jyh Harn, Tzyy-Wen Chiou, Ming-Hsi Chuang, Chun-Hung Chen, Chi-Hsuan Chuang, Po-Cheng Lin, Shinn-Zong LinAbstractLeft ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an est...
Source: Redox Biology - March 22, 2019 Category: Biology Source Type: research

Mitochondria-associated lactate dehydrogenase is not a biologically significant contributor to bioenergetic function in murine striated muscle
Publication date: Available online 22 March 2019Source: Redox BiologyAuthor(s): Kyle L. Fulghum, Benjamin R. Rood, Velma O. Shang, Lindsey A. McNally, Daniel W. Riggs, Yu-Ting Zheng, Bradford G. HillAbstractPrevious studies indicate that mitochondria-localized lactate dehydrogenase (mLDH) might be a significant contributor to metabolism. In the heart, the presence of mLDH could provide cardiac mitochondria with a higher capacity to generate reducing equivalents directly available for respiration, especially during exercise when circulating lactate levels are high. The purpose of this study was to test the hypothesis that m...
Source: Redox Biology - March 22, 2019 Category: Biology Source Type: research

Targeting immune cells for cancer therapy
Publication date: Available online 20 March 2019Source: Redox BiologyAuthor(s): Sin Yee Gun, Sharon Wei Ling Lee, Je Lin Sieow, Siew Cheng WongAbstractRecent years have seen a renaissance in the research linking inflammation and cancer with immune cells playing a central role in smouldering inflammation in the tumor microenvironment. Diverse immune cell types infiltrate the tumor microenvironment, and the dynamic tumor-immune cell interplay gives rise to a rich milieu of cytokines and growth factors. Fundamentally, this intricate cross-talk creates the conducive condition for tumor cell proliferation, survival and metastas...
Source: Redox Biology - March 21, 2019 Category: Biology Source Type: research

Phenothiazine normalizes the NADH/NAD+ ratio, maintains mitochondrial integrity and protects the nigrostriatal dopamine system in a chronic rotenone model of Parkinson's disease
This study aimed to identify disease-modifying treatments for PD. Unsubstituted phenothiazine (PTZ) is a small and uncharged aromatic imine that readily crosses the blood-brain barrier. PTZ lacks significant DA receptor-binding activity and, in the nanomolar range, exhibits protective effects via its potent free radical scavenging and anti-inflammatory activities. Given that DAergic neurons are highly vulnerable to oxidative damage and inflammation, we hypothesized that administration of PTZ might confer neuroprotection in different experimental models of PD. Our findings showed that PTZ rescues rotenone (ROT) toxicity in ...
Source: Redox Biology - March 21, 2019 Category: Biology Source Type: research

Interactions between plasma copper concentrations and SOD1 gene polymorphism for impaired glucose regulation and type 2 diabetes
Publication date: Available online 18 March 2019Source: Redox BiologyAuthor(s): Jiawei Yin, Xiaoqian Wang, Shuzhen Li, Yalun Zhu, Sijing Chen, Peiyun Li, Cheng Luo, Yue Huang, Xiaoqin Li, Xueting Hu, Wei Yang, Wei Bao, Zhilei Shan, Liegang LiuAbstractAimsTo examine the associations of plasma copper concentrations and superoxide dismutase 1 (SOD1) polymorphisms as well as their gene-environment interaction with newly diagnosed impaired glucose regulation (IGR) and type 2 diabetes (T2D).MethodsWe performed a large case-control study in 2520 Chinese Han subjects: 1004 newly diagnosed T2D patients, 512 newly diagnosed IGR pati...
Source: Redox Biology - March 19, 2019 Category: Biology Source Type: research

2-O-β-d-glucopyranosyl-l-ascorbic acid, a novel vitamin C derivative from Lycium barbarum, prevents oxidative stress
Publication date: Available online 18 March 2019Source: Redox BiologyAuthor(s): Shen-Fei Wang, Xin Liu, Mo-Yu Ding, Shuangcheng Ma, Jing Zhao, Ying Wang, Shaoping LiAbstractReducing agents are crucial for the management of maladaptive inflammation-induced macrophage death and hematopoietic toxicity of chemotherapy. 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), a unique AA (or vitamin C) derivative identified in Lycium barbarum, exhibited enhanced free radical scavenging activity compared with AA and its synthetic derivative AA-2αG. AA-2βG protected hydrogen peroxide-induced cell death in murine macr...
Source: Redox Biology - March 19, 2019 Category: Biology Source Type: research

The glutathione system and the related thiol network in Caenorhabditis elegans
Publication date: Available online 16 March 2019Source: Redox BiologyAuthor(s): Gavin Douglas Ferguson, Wallace John BridgeAbstractAdvances in the field of redox biology have contributed to the understanding of the complexity of the thiol-based system in mediating signal transduction. The redox environment is the overall spatiotemporal balance of oxidation-reduction systems within the integrated compartments of the cell, tissues and whole organisms. The ratio of the reduced to disulfide glutathione redox couple (GSH:GSSG) is a key indicator of the redox environment and its associated cellular health. The reaction mechanism...
Source: Redox Biology - March 18, 2019 Category: Biology Source Type: research

Peroxisomal regulation of redox homeostasis and adipocyte metabolism
Publication date: Available online 14 March 2019Source: Redox BiologyAuthor(s): Jingjing Liu, Wen Lu, Bimin Shi, Samuel Klein, Xiong SuAbstractPeroxisomes are ubiquitous cellular organelles required for specific pathways of fatty acid oxidation and lipid synthesis, and until recently their functions in adipocytes have not been well appreciated. Moreover, peroxisomes host many oxygen-consumption reactions and play a major role in generation and detoxification of reactive oxygen species (ROS) and reactive nitrogen species (RNS), influencing whole cell redox status. Here, we review recent progress in peroxisomal functions in ...
Source: Redox Biology - March 15, 2019 Category: Biology Source Type: research

Nitric oxide-donor/PARP-inhibitor combination: A new approach for sensitization to ionizing radiation
Publication date: Available online 15 March 2019Source: Redox BiologyAuthor(s): Aaron Wilson, Vijay Menon, Zubair Khan, Asim Alam, Larisa Litovchick, Vasily YakovlevAbstractRecently, clinical development of PARP inhibitors (PARPi) expanded from using them as a single agent to combining them with DNA-damaging therapy to derive additional therapeutic benefit from stimulated DNA damage. Furthermore, inhibiting PARP in cancers with BRCA1/2 mutations has been shown to be an effective synthetic lethality approach either as a single agent or in combination with the different DNA damaging agents: chemotherapy or ionizing radiation...
Source: Redox Biology - March 15, 2019 Category: Biology Source Type: research

Monitoring structural modulation of redox-sensitive proteins in cells with MS-CETSA
Publication date: Available online 14 March 2019Source: Redox BiologyAuthor(s): Wendi Sun, Lingyun Dai, Han Yu, Brenda Puspita, Tianyun Zhao, Feng Li, Justin L. Tan, Yan Ting Lim, Ming Wei Chen, Radoslaw M. Sobota, Daniel G. Tenen, Nayana Prabhu, Pär NordlundAbstractReactive oxygen species (ROS) induce different cellular stress responses but can also mediate cellular signalling. Augmented levels of ROS are associated with aging, cancer as well as various metabolic and neurological disorders. ROS can also affect the efficacy and adverse effects of drugs. Although proteins are key mediators of most ROS effects, direct s...
Source: Redox Biology - March 15, 2019 Category: Biology Source Type: research

The vitamin E derivative garcinoic acid from Garcinia kola nut seeds attenuates the inflammatory response
This study outlines an optimized procedure for the extraction and purification of GA from Garcinia kola seeds with an increased yield and a purity of>99%. We found that LPS-induced upregulation of iNos and Cox2 expression, and the formation of the respective signaling molecules nitric oxide and prostanoids, were significantly diminished by both the NE and GA. In addition, GA treatment in mice decreased intra-plaque inflammation by attenuating nitrotyrosinylation. Further, modulation of lymphocyte sub-populations in blood and spleen have been detected, showing immune regulative properties of GA.Our study provides molecul...
Source: Redox Biology - March 13, 2019 Category: Biology Source Type: research

c-Myc activation promotes cofilin-mediated F-actin cytoskeleton remodeling and telomere homeostasis as a response to oxidant-based DNA damage in medulloblastoma cells
Publication date: Available online 13 March 2019Source: Redox BiologyAuthor(s): Anna Lewinska, Jolanta Klukowska-Rötzler, Anna Deregowska, Jagoda Adamczyk-Grochala, Maciej WnukAbstractMedulloblastoma (MB) is a common and highly aggressive pediatric brain tumor of a heterogeneous nature. According to transcriptome-based profiling, four molecular subgroups of MB have been revealed, namely WNT, SHH, Group 3 and Group 4. High MYC mRNA expression and MYC gene amplification in MB have been considered as indicators of poor prognosis. However, the role of c-Myc in MB biology is still not well established. In the present study...
Source: Redox Biology - March 13, 2019 Category: Biology Source Type: research

Restoration of aberrant mTOR signaling by intranasal rapamycin reduces oxidative damage: Focus on HNE-modified proteins in a mouse model of down syndrome
Publication date: Available online 9 March 2019Source: Redox BiologyAuthor(s): Fabio Di Domenico, Antonella Tramutola, Eugenio Barone, Chiara Lanzillotta, Olivia Defever, Andrea Arena, Ilaria Zuliani, Cesira Foppoli, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D. Allan Butterfield, Marzia PerluigiAbstractIncreasing evidences support the notion that the impairment of intracellular degradative machinery is responsible for the accumulation of oxidized/misfolded proteins that ultimately results in the deposition of protein aggregates. These events are key pathological aspects of “protein misfolding diseas...
Source: Redox Biology - March 11, 2019 Category: Biology Source Type: research

CNS function and dysfunction during exposure to hyperbaric oxygen in operational and clinical settings
Publication date: Available online 9 March 2019Source: Redox BiologyAuthor(s): Geoffrey E. Ciarlone, Christopher M. Hinojo, Nicole M. Stavitzski, Jay B. DeanAbstractHyperbaric oxygen (HBO2) is breathed during hyperbaric oxygen therapy and during certain undersea pursuits in diving and submarine operations. What limits exposure to HBO2 in these situations is the acute onset of central nervous system oxygen toxicity (CNS-OT) following a latent period of safe oxygen breathing. CNS-OT presents as various non-convulsive signs and symptoms, many of which appear to be of brainstem origin involving cranial nerve nuclei and autonom...
Source: Redox Biology - March 11, 2019 Category: Biology Source Type: research

Mitochondria in precision medicine; linking bioenergetics and metabolomics in platelets
Publication date: Available online 10 March 2019Source: Redox BiologyAuthor(s): Balu K. Chacko, Matthew R. Smith, Michelle S. Johnson, Gloria Benavides, Matilda L. Culp, Jyotsna Pilli, Sruti Shiva, Karan Uppal, Young-Mi Go, Dean P. Jones, Victor M. Darley-UsmarAbstractMitochondria possess reserve bioenergetic capacity, supporting protection and resilience in the face of disease. Approaches are limited to understand factors that impact mitochondrial functional reserve in humans. We applied the mitochondrial stress test (MST) to platelets from healthy subjects and found correlations between energetic parameters and mitochond...
Source: Redox Biology - March 11, 2019 Category: Biology Source Type: research

Short term Pm2.5 exposure caused a robust lung inflammation, vascular remodeling, and exacerbated transition from left ventricular failure to right ventricular hypertrophy
Publication date: Available online 6 March 2019Source: Redox BiologyAuthor(s): Wenhui Yue, Lei Tong, Xiaohong Liu, Xinyu Weng, Xiaoyu Chen, Dongzhi Wang, Samuel C. Dudley, E. Kenneth Weir, Wenjun Ding, Zhongbing Lu, Yawei Xu, Yingjie ChenAbstractHeart failure (HF) is the single largest cause for increased hospitalization after fine particulate matter (PM2.5) exposure. Patients with left HF often progress to right ventricular (RV) failure even with optimal medical care. An increase of PM2.5 of 10 μg per cubic meter was associated with a 76% increase in the risk of death from cardiovascular disease in 4 years' period. H...
Source: Redox Biology - March 8, 2019 Category: Biology Source Type: research

Corrigendum to “Mitofusin1 in oocyte is essential for female fertility” [Redox Biol. 21 (2019) 101110]
Publication date: Available online 7 March 2019Source: Redox BiologyAuthor(s): Xiaojing Hou, Shuai Zhu, Hao Zhang, Chunling Li, Danhong Qiu, Juan Ge, Xuejiang Guo, Qiang Wang (Source: Redox Biology)
Source: Redox Biology - March 8, 2019 Category: Biology Source Type: research

Peperomin E and its orally bioavailable analog induce oxidative stress-mediated apoptosis of acute myeloid leukemia progenitor cells by targeting thioredoxin reductase
Publication date: Available online 8 March 2019Source: Redox BiologyAuthor(s): Xinzhi Wang, Ming Gao, Jiyun Zhang, Ying Ma, Wenshu Qu, Jiangyu Liang, Hao Wu, Hongmei WenAbstractThe early immature CD34+ acute myeloid leukemia (AML) cell subpopulation-acute myeloid leukemia progenitor cells (APCs), is often resistant to conventional chemotherapy, making them largely responsible for the relapse of AML. However, to date, the eradication of APCs remains a major challenge. We previously reported a naturally occurring secolignan- Peperomin E (PepE) and its analog 6-methyl (hydroxyethyl) amino-2, 6-dihydropeperomin E (DMAPE) that ...
Source: Redox Biology - March 8, 2019 Category: Biology Source Type: research

Improved mass spectrometry-based activity assay reveals oxidative and metabolic stress as sirtuin-1 regulators
Publication date: Available online 5 March 2019Source: Redox BiologyAuthor(s): Di Shao, Chunxiang Yao, Maya H. Kim, Jessica Fry, Richard A. Cohen, Catherine E. Costello, Reiko Matsui, Francesca Seta, Mark E. McComb, Markus M. BachschmidAbstractSirtuin-1 (SirT1) catalyzes NAD+-dependent protein lysine deacetylation and is a critical regulator of energy and lipid metabolism, mitochondrial biogenesis, apoptosis, and senescence. Activation of SirT1 mitigates metabolic perturbations associated with diabetes and obesity. Pharmacologic molecules, cellular redox, and nutritional states can regulate SirT1 activity.Technical barrier...
Source: Redox Biology - March 6, 2019 Category: Biology Source Type: research

Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype
Publication date: Available online 6 March 2019Source: Redox BiologyAuthor(s): Mayumi Fujita, Veena Somasundaram, Debashree Basudhar, Robert Y.S. Cheng, Lisa A. Ridnour, Harumi Higuchi, Kaori Imadome, Jae Hong No, Gaurav Bharadwaj, David A. WinkAbstractPancreatic cancer is a highly metastatic tumor with an extremely low 5-year survival rate. Lack of efficient diagnostics and dearth of effective therapeutics that can target the cancer as well as the microenvironment niche are the reasons for limited success in treatment and management of this disease. Cell invasion through extracellular matrix (ECM) involves the complex reg...
Source: Redox Biology - March 6, 2019 Category: Biology Source Type: research

Age-related oxidative stress confines damage-responsive Bmi1+ cells to perivascular regions in the murine adult heart
Publication date: Available online 4 March 2019Source: Redox BiologyAuthor(s): Diego Herrero, Susana Cañón, Guillermo Albericio, Rosa María Carmona, Susana Aguilar, Santos Mañes, Antonio BernadAbstractAdult progenitor cells reside in specialized microenvironments which maintain their undifferentiated cell state and trigger regenerative responses following injury. Although these environments are well described in several tissues, the cellular components that comprise the cardiac environment where progenitor cells are located remain unknown. Here we use Bmi1CreERT and Bmi1GFP mice as genetic tools...
Source: Redox Biology - March 5, 2019 Category: Biology Source Type: research

Age-related loss of mitochondrial glutathione exacerbates menadione-induced inhibition of Complex I
Publication date: Available online 2 March 2019Source: Redox BiologyAuthor(s): Nicholas O. Thomas, Kate P. Shay, Tory M. HagenAbstractThe role of mitochondrial GSH (mGSH) in the enhanced age-related susceptibility to xenobiotic toxicity is not well defined. We determined mGSH status and indices of mitochondrial bioenergetics in hepatocytes from young and old F344 rats treated with 300 μM menadione, a concentration that causes 50% cell death in old. At this concentration, mGSH was significantly lost only in hepatocytes from old rats, and with near total depletion due to lower basal mGSH in aged cells. In old hepatocyte...
Source: Redox Biology - March 4, 2019 Category: Biology Source Type: research

TRIM69 inhibits cataractogenesis by negatively regulating p53
In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.Graphical abstract (Source: Redox Biology)
Source: Redox Biology - March 4, 2019 Category: Biology Source Type: research

Critical role of AMPK in redox regulation under glucose starvation
Publication date: Available online 2 March 2019Source: Redox BiologyAuthor(s): Yi Ren, Han-Ming ShenAbstractGlucose starvation is one of the major forms of metabolic stress in cancer cells. Deprivation of glucose impairs glycolysis and the pentose phosphate pathway, which elicits oxidative stress due to enhanced production of reactive oxygen species (ROS) and impaired antioxidant system, leading to redox imbalance and cell death. Under glucose starvation, the 5′ AMP-activated protein kinase (AMPK) plays a critical role in maintaining redox homeostasis and cell survival via multiple pathways, such as regulation of fat...
Source: Redox Biology - March 4, 2019 Category: Biology Source Type: research