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Source: Free Radical Biology and Medicine

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Total 199 results found since Jan 2013.

Epigenetic modifications of Nrf2-mediated glutamate cysteine ligase: Implications in the development of diabetic retinopathy and in the metabolic memory phenomenon associated with its continued progression.
Abstract Diabetes increases oxidative stress in the retina and decreases the levels of intracellular antioxidant, GSH. Transcriptional factor Nrf2 regulates the expression of Gclc, the enzyme important in the biosynthesis of GSH, and in diabetes the binding of Nrf2 at the antioxidant response element region 4 (ARE4) is decreased. Our aim is to investigate the role of epigenetic modifications in the decreased Nrf2 binding at Gclc-ARE4 in the development of diabetic retinopathy, and in the metabolic memory associated with its continued progression. Effect of hyperglycemia on H3K4 methylation on Nrf2 binding at Gclc-...
Source: Free Radical Biology and Medicine - July 9, 2014 Category: Biology Authors: Mishra M, Zhong Q, Kowluru RA Tags: Free Radic Biol Med Source Type: research

N(ε)-carboxymethyllysine mediated ER stress promotes endothelial cell injury through Nox4/MKP-3 interaction.
We examined whether ER localization of MAPK phosphatase-3 (MKP-3) is critical in regulating ERK inactivation and promotes NADPH oxidase-4 (Nox4) activation in CML-induced endothelial cell injury. We demonstrated that serum CML levels were significantly increased in type 2 diabetes patients and diabetic animals. CML induced ER stress and apoptosis, reduced ERK activation, and increased MKP-3 protein activity in HUVECs and SVECs. MKP-3 siRNA transfection, but not MKP-1 or MKP-2, abolished the effects of CML on HUVECs. Nox4-mediated activation of MKP-3 regulated the switch to ERK de-phosphorylation. CML also increased the int...
Source: Free Radical Biology and Medicine - July 8, 2014 Category: Biology Authors: Lee WJ, Huey-Herng Sheu W, Liu SH, Yi YC, Chen WC, Lin SY, Liang KW, Shen CC, Yeh HY, Lin LY, Tsai YC, Tien HR, Lee MR, Yang TJ, Sheu ML Tags: Free Radic Biol Med Source Type: research

Exendin-4 protects adipose-derived mesenchymal stem cells from apoptosis induced by hydrogen peroxide through the PI3K/Akt-Sfrp2 pathways.
Abstract Adipose-derived mesenchymal stem cells (ADMSCs)-based therapy is a promising modality for the treatment of myocardial infarction in the future. However, the majority of transplanted cells are readily lost after transplantation because of hypoxia and oxidative stress. An efficient means to enhance the ability of ADMSCs to survive under pathologic conditions is required. In our study, we explored the effects of exendin-4 (Ex-4) on ADMSCs apoptosis in vitro induced by hydrogen peroxide, focusing in particular on mitochondrial apoptotic pathways and PI3K/Akt-secreted frizzled-related protein 2 (Sfrp2) surviva...
Source: Free Radical Biology and Medicine - October 16, 2014 Category: Biology Authors: Zhou H, Yang J, Xin T, Li D, Guo J, Hu S, Zhou S, Zhang T, Zhang Y, Han T, Chen Y Tags: Free Radic Biol Med Source Type: research

Ochratoxin A promotes porcine circovirus type 2 replication in vitro and in vivo.
Abstract Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin in animals and humans. Porcine circovirus-associated disease (PCVAD), including porcine dermatitis and nephropathy syndrome, is a worldwide swine disease. To date, little is known concerning the relationship between OTA and porcine circovirus type 2 (PCV2), the primary causative agent of PCVAD. Effects of OTA on PCV2 replication and its mechanism were investigated in vitro and in vivo. The results in vitro showed that low doses of OTA significantly increased PCV2 DNA copies and the number of infected cells. Maximum ...
Source: Free Radical Biology and Medicine - December 23, 2014 Category: Biology Authors: Gan F, Zhang Z, Hu Z, Hesketh J, Xue H, Chen X, Hao S, Huang Y, Cole Ezea P, Parveen F, Huang K Tags: Free Radic Biol Med Source Type: research

PPARγ depletion stimulates Nox4 expression and human pulmonary artery smooth muscle cell proliferation.
Abstract Hypoxia stimulates pulmonary hypertension (PH) in part by increasing the proliferation of pulmonary vascular wall cells. Recent evidence suggests that signaling events involved in hypoxia-induced cell proliferation include sustained nuclear factor-kappaB (NF-κB) activation, increased NADPH oxidase 4 (Nox4) expression, and downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) levels. To further understand the role of reduced PPARγ levels associated with PH pathobiology, siRNA was employed to reduce PPARγ levels in human pulmonary artery smooth muscle cells (HPASMC) in vitro under n...
Source: Free Radical Biology and Medicine - December 31, 2014 Category: Biology Authors: Bijli KM, Kleinhenz JM, Murphy TC, Kang B, Adesina SE, Sutliff RL, Hart CM Tags: Free Radic Biol Med Source Type: research

Lipid peroxidation product 4-Hydroxy-trans-2-nonenal (HNE) causes protein synthesis in cardiac myocytes via activated mTORC1-P70S6K-RPS6 signaling.
Abstract Reactive oxygen species (ROS) are elevated in the heart in response to hemodynamic and metabolic stress, and promote hypertrophic signaling. ROS also mediate the formation of lipid peroxidation-derived aldehydes that may promote myocardial hypertrophy. One lipid peroxidation byproduct, 4-Hydroxy-trans-2-nonenal (HNE), is a reactive aldehyde that covalently modifies proteins thereby altering their function. HNE adducts directly inhibit the activity of LKB1, a serine/threonine kinase involved in regulating cellular growth in part through its interaction with the AMP-activated protein kinase (AMPK), but whet...
Source: Free Radical Biology and Medicine - January 21, 2015 Category: Biology Authors: Calamaras TD, Lee C, Lan F, Ido Y, Siwik DA, Colucci WS Tags: Free Radic Biol Med Source Type: research

TNF-α inhibitor protects against myocardial ischemia/reperfusion injury via Notch1 mediated suppression of oxidative/nitrative stress.
This study aims to determine the involvement of TNF-a inhibitor with Notch1 in MI/R and delineate the related mechanism. Notch1 specific small interfering RNA (siRNA, 20μg) or Jagged1 (a Notch ligand, 12μg) was delivered through intramyocardial injection. 48h after injection, mice received 30min of myocardial ischemia followed by 3h (for cell apoptosis and oxidative/nitrative stress) and 24h (for infarct size and cardiac function) of reperfusion. 10min before reperfusion, mice randomly received intraperitoneal injection of vehicle, Etanercept, diphenyleneiodonium, 1400W or EUK134. Finally, downregulation of Notch1 signif...
Source: Free Radical Biology and Medicine - February 10, 2015 Category: Biology Authors: Pei H, Song X, Peng C, Tan Y, Li Y, Li X, Ma S, Wang Q, Huang R, Yang D, Li, Gao E, Yang Y Tags: Free Radic Biol Med Source Type: research

MKK3 mediates inflammatory response through modulation of mitochondrial function.
Abstract Mitochondria are increasingly recognized as drivers of inflammatory responses. MAP kinase kinase 3 (MKK3), a dual-specificity protein kinase, is activated in inflammation and in turn activates p38 MAP kinase signaling. Here we show that MKK3 influences mitochondrial function and acts as a critical mediator of inflammation. MKK3 deficient (MKK3(-/-)) mice and bone marrow derived macrophages (BMDMs) secreted less cytokines than wild type (WT) after LPS exposure. There was improved mitochondrial function, as measured by basal oxygen consumption rate, mitochondrial membrane potential, and ATP production, in M...
Source: Free Radical Biology and Medicine - February 16, 2015 Category: Biology Authors: Srivastava A, Shinn AS, Lee PJ, Mannam P Tags: Free Radic Biol Med Source Type: research

Pterostilbene and allopurinol reduce fructose-induced podocyte oxidative stress and inflammation via microRNA-377.
Abstract High dietary fructose is an important causative factor in the development of metabolic syndrome-associated glomerular podocyte oxidative stress and injury. Here, we identified microRNA-377 (miR-377) as a biomarker of oxidative stress in renal cortex of fructose-fed rats, which correlated with podocyte injury and albuminuria in metabolic syndrome. Fructose feeding increased miR-377 expression and decreased superoxide dismutase (SOD) expression and activity, caused O2(•-) and H2O2 over-production in kidney cortex or glomeruli of rats. This ROS induction increased p38 MAPK phosphorylation and thioredoxin-i...
Source: Free Radical Biology and Medicine - March 4, 2015 Category: Biology Authors: Wang W, Ding XQ, Gu TT, Song L, Li JM, Xue QC, Kong LD Tags: Free Radic Biol Med Source Type: research

Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition.
Abstract We previously reported the promising effect of dioscin against hepatic ischemia /reperfusion (I/R) injury, but its effect on cerebral I/R injury remains unknown. In this work, an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model and an in vivo middle cerebral artery occlusion (MCAO) model were used. The results indicated that dioscin clearly protected PC12 cells and primary cortical neurons against OGD/R insult and significantly prevented cerebral I/R injury. Further research demonstrated that dioscin-induced neuroprotection was accompanied by a significant inhibition in the expression a...
Source: Free Radical Biology and Medicine - March 12, 2015 Category: Biology Authors: Tao X, Sun X, Yin L, Han X, Xu L, Qi Y, Xu Y, Li H, Lin Y, Liu K, Peng J Tags: Free Radic Biol Med Source Type: research

Essential role of NRF2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes.
In conclusion, our work has revealed that in hepatocytes, Nrf2 is an essential early player in the rescue of oxidative stress by LA leading to protection against PA-mediated lipoapoptosis. PMID: 25841776 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - April 1, 2015 Category: Biology Authors: Pilar Valdecantos M, Prieto-Hontoria PL, Pardo V, Módol T, Santamaría B, Weber M, Herrero L, Serra D, Muntané J, Cuadrado A, Moreno-Aliaga MJ, Alfredo Martínez J, Valverde ÁM Tags: Free Radic Biol Med Source Type: research

The superoxide dismutase 1 (SOD1) 3'UTR maintains High expression of the SOD1 gene in Cancer cells: The involvement of the RNA binding protein AUF1.
In this study, a full-length 3'UTR of the SOD1 transcript was cloned and characterized for its ability to regulate SOD1 gene expression in human cancer cells. Inclusion of the SOD1 3'UTR in the pGL3 reporter construct dramatically enhanced the reporter activity by 10-220-fold in various cell lines. RT-PCR analysis, however, indicated that the reporter gene mRNA levels were only modestly altered by the SOD1 3'UTR, suggesting that SOD1 3'UTR enhances the reporter gene activity not simply by stabilizing the mRNA but primarily through promoting translation of the protein. Bioinformatics analysis showed multiple stem and loop s...
Source: Free Radical Biology and Medicine - April 20, 2015 Category: Biology Authors: Zhang S, Xue J, Zheng J, Wang S, Zhou J, Jiao Y, Geng Y, Wu J, Hannafon BN, Ding WQ Tags: Free Radic Biol Med Source Type: research

UCP2 inhibition sensitizes breast Cancer cells to therapeutic agents by increasing oxidative stress.
In conclusion, UCP2 could be a therapeutic target in breast cancer, especially in those patients treated with tamoxifen. PMID: 25960046 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - May 7, 2015 Category: Biology Authors: Pons DG, Nadal-Serrano M, Torrens-Mas M, Valle A, Oliver J, Roca P Tags: Free Radic Biol Med Source Type: research

c-jun N-terminal kinase attenuates TNFα signaling by reducing Nox1-dependent endosomal ROS production in vascular smooth muscle cells.
Abstract Tumor necrosis factor-α (TNFα), a pro-inflammatory cytokine, causes vascular smooth muscle cell (VSMC) proliferation and migration and promotes inflammatory vascular lesions. Nuclear factor-kappa B (NF-κB) activation by TNFα requires endosomal superoxide production by Nox1. In endothelial cells, TNFα stimulates c-Jun N-terminal kinase (JNK), which inhibits NF-κB signaling. The mechanism by which JNK negatively regulates TNFα-induced NF-κB activation has not been defined. We hypothesized that JNK modulates NF-κB activation in VSMC, and does so via a Nox1-dependent mechanism. TNFα-induced NF-κB a...
Source: Free Radical Biology and Medicine - May 19, 2015 Category: Biology Authors: Choi H, Dikalova A, Stark RJ, Lamb FS Tags: Free Radic Biol Med Source Type: research

Molecular Hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor knockout mice.
CONCLUSIONS: The inhibitory effects of H2 on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of ERS pathway and by activating Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability. PMID: 26117323 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - June 24, 2015 Category: Biology Authors: Song G, Zong C, Zhang Z, Yu Y, Yao S, Jiao P, Tian H, Zhai L, Zhao H, Tian S, Zhang X, Wu Y, Sun X, Qin S Tags: Free Radic Biol Med Source Type: research