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Source: Free Radical Biology and Medicine

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Total 199 results found since Jan 2013.

Age-Dependent Oxidation of Extracellular Cysteine/Cystine Redox State (Eh(Cys/CySS)) in Mouse Lung Fibroblasts is Mediated by a Decline in Slc7a11 Expression.
In conclusion, our study reveals Slc7a11 is the key regulator of age-dependent changes in extracellular Eh(Cys/CySS) in primary mouse lung fibroblasts, and its effects are not dependent on GSH synthesis. PMID: 29458149 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - February 16, 2018 Category: Biology Authors: Zheng Y, Ritzenthaler JD, Burke TJ, Otero J, Roman J, Watson WH Tags: Free Radic Biol Med Source Type: research

Nox4 regulates the eNOS uncoupling process in aging endothelial cells.
Abstract ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chap...
Source: Free Radical Biology and Medicine - September 12, 2017 Category: Biology Authors: Lee HY, Kim HR, Chae HJ Tags: Free Radic Biol Med Source Type: research

Nitric oxide donor Ru(terpy)(bdq)NO(3+) induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production.
Abstract [Ru(terpy)(bdq)NO](3+) (TERPY) is a nitric oxide (NO) donor that promotes relaxation of the mesenteric artery and aorta in rats. We sought to investigate whether it acts as both an NO donor and endothelial NO synthase (eNOS) activator, as shown previously for nitroglycerin. Human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 cells transfected with empty vector (HEK) or eNOS cDNA (HEK-eNOS) were treated with TERPY (1µM) for different lengths of time. eNOS expression, dimerization, and Ser(1177) phosphorylation, caveolin-1 (Cav-1) oligomerization, Cav-1 Tyr(14) phosphorylation we...
Source: Free Radical Biology and Medicine - September 9, 2017 Category: Biology Authors: Potje SR, Chen Z, Oliveira SDS, Bendhack LM, da Silva RS, Bonini MG, Antoniali C, Minshall RD Tags: Free Radic Biol Med Source Type: research

Lysocardiolipin Acyltransferase Regulates TGF- β Mediated Lung Fibroblast Differentiation.
In this study, we investigated the role of LYCAT in TGF-β mediated differentiation of human lung fibroblasts to myofibroblasts, and whether this occurred through mitochondrial superoxide and NOX4 mediated hydrogen peroxide (H2O2) generation. Our data indicated that LYCAT expression was up-regulated in primary lung fibroblasts isolated from IPF patients and bleomycin-challenged mice, compared to controls. In vitro, siRNA-mediated SMAD3 depletion inhibited TGF-β stimulated LYCAT expression in human lung fibroblasts. ChIP immunoprecipitation assay revealed TGF-β stimulated SMAD2/3 binding to the endogenous LYCAT promoter, ...
Source: Free Radical Biology and Medicine - July 24, 2017 Category: Biology Authors: Huang LS, Jiang P, Feghali-Bostwick C, Reddy SP, Garcia JGN, Natarajan V Tags: Free Radic Biol Med Source Type: research

ROS-dependent activation of RhoA/Rho-kinase in pulmonary artery: Role of Src-family kinases and ARHGEF1.
Abstract The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses we...
Source: Free Radical Biology and Medicine - June 30, 2017 Category: Biology Authors: MacKay CE, Shaifta Y, Snetkov VV, Francois AA, Ward JPT, Knock GA Tags: Free Radic Biol Med Source Type: research

Endogenous hydrogen sulfide-mediated MAPK inhibition preserves endothelial function through TXNIP signaling.
Abstract Mounting evidence demonstrated deficient cystathionine-γ-lyase (CSE)/H2S implicated the development of cardiovascular disease. The present study aimed to evaluating the favorable action of CSE derived H2S on endothelial function in CSE(-/-) mice. CSE(-/-) mice exhibited attenuated endothelium-dependent relaxations, coupled with reduction of endothelial nitric oxide synthase (eNOS) phosphorylation at site of Ser1177, increase of thioredoxin interacting protein (TXNIP) level and MAPK phosphorylation, which were corrected by sodium hydrosulfide chronic treatment for 8 weeks. Impaired relaxations to ACh and ...
Source: Free Radical Biology and Medicine - June 29, 2017 Category: Biology Authors: Tian D, Dong J, Jin S, Teng X, Wu Y Tags: Free Radic Biol Med Source Type: research

Endothelial deletion of mTORC1 protects against hindlimb ischemia in diabetic mice via activation of autophagy, attenuation of oxidative stress and alleviation of inflammation.
In conclusion, our present study demonstrates that endothelial mTORC1 deletion protects against hindlimb ischemic injury in diabetic mice possibly via activation of autophagy, attenuation of oxidative stress and alleviation of inflammation. Therapeutics targeting mTORC1 may therefore represents a promising strategy to rescue limb ischemia in diabetes mellitus. PMID: 28473248 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - May 1, 2017 Category: Biology Authors: Fan W, Han D, Sun Z, Ma S, Gao L, Chen J, Li X, Li X, Fan M, Li C, Hu D, Wang Y, Cao F Tags: Free Radic Biol Med Source Type: research

Epigallocatechin Gallate Upregulates NRF2 to Prevent Diabetic Nephropathy via Disabling KEAP1.
Abstract Epigallocatechin gallate (EGCG) is the most abundant and effective green tea catechin and has been reported to attenuate diabetic nephropathy (DN). However, the mechanism by which EGCG ameliorates DN, till now, has remained unclear. EGCG is known as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defense against diabetes-induced oxidative stress and in the prevention of DN. In the present study, we tested whether NRF2 is required for EGCG protection against DN. Therefore, C57BL/6 wild type (WT) and Nrf2 knockout mice were induced to diabetes by ...
Source: Free Radical Biology and Medicine - April 27, 2017 Category: Biology Authors: Sun W, Liu X, Zhang H, Song Y, Li T, Liu X, Liu Y, Guo L, Wang F, Yang T, Guo W, Wu J, Jin H, Wu H Tags: Free Radic Biol Med Source Type: research

SERPINB1 Ameliorates Acute Lung Injury in Liver Transplantation Through ERK1/2-mediated STAT3-dependent HO-1 Induction.
CONCLUSIONS: SERPINB1 decreased inflammation, ameliorated oxidative stress in the lung, and attenuated ALI in rats with OALT by activating HO-1 and it does so through STAT3 and it does so by activating ERK1/2. PMID: 28427999 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - April 17, 2017 Category: Biology Authors: Yao W, Li H, Luo G, Li X, Chen C, Yuan D, Chi X, Xia Z, Hei Z Tags: Free Radic Biol Med Source Type: research

O-Aminobenzoyl-S-Nitrosoglutathione: a Fluorogenic, Cell Permeable, Pseudo-Substrate for S-Nitrosoglutathione Reductase.
Abstract S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD(+)-dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the spontaneous reaction between formaldehyde and glutathione). While initially recognized as the enzyme that is involved in formaldehyde detoxification, increasing amount of research evidence has shown that GSNOR also plays a significant role in nitric oxide mediated signaling through its modulation of protein S-nitrosothiol abundance via transnitrosation reactions with GSN...
Source: Free Radical Biology and Medicine - April 15, 2017 Category: Biology Authors: Sun BL, Palmer L, Alam SR, Adekoya I, Brown-Steinke K, Periasamy A, Mutus B Tags: Free Radic Biol Med Source Type: research

Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells.
In this study, a RIP1/RIP3 complex was formed in 2-methoxy-6-acetyl-7-methyljuglone (MAM)-treated HCT116 and HT29 colon cancer cells. With this formation, mitochondrial reactive oxygen species (ROS) levels increased, mitochondrial depolarization occurred, and ATP concentrations decreased. This process was identified as necroptosis. This finding was confirmed by experiments showing that MAM-induced cell death was attenuated by the pharmacological or genetic blockage of necroptosis signaling, including RIP1 inhibitor necrostatin-1s (Nec-1s) and siRNA-mediated gene silencing of RIP1 and RIP3, but was unaffected by caspase inh...
Source: Free Radical Biology and Medicine - April 14, 2017 Category: Biology Authors: Sun W, Wu X, Gao H, Yu J, Zhao W, Lu JJ, Wang J, Du G, Chen X Tags: Free Radic Biol Med Source Type: research

Zinc Regulates Nox1 Expression Through a NF- κB and Mitochondrial ROS Dependent Mechanism to Induce Senescence of Vascular Smooth Muscle Cells.
CONCLUSION: Our data demonstrate that altered zinc distribution leading to accumulation of zinc in the mitochondria increases mitochondrial ROS production causing NF-κB activation which in turn upregulates Nox1 expression inducing senescence of VSMCs. PMID: 28363602 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - March 29, 2017 Category: Biology Authors: Salazar G, Huang J, Feresin RG, Zhao Y, Griendling KK Tags: Free Radic Biol Med Source Type: research

Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo αpyrene.
CONCLUSION: A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors. PMID: 28300668 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - March 11, 2017 Category: Biology Authors: Kalthoff S, Landerer S, Reich J, Strassburg CP Tags: Free Radic Biol Med Source Type: research

Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes.
Abstract Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1β-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE2, iNOS and NO in IL-1β-stimulated OA chondrocytes. Further, Wogonin exhibits potent chondroprotective potential by switching the signaling axis of matrix degradation from cata...
Source: Free Radical Biology and Medicine - February 21, 2017 Category: Biology Authors: Khan NM, Haseeb A, Ansari MY, Devarapalli P, Haynie S, Haqqi TM Tags: Free Radic Biol Med Source Type: research

CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk.
In this study, we found the chemotherapy agent SN-38 induced autophagy in colorectal cancer (CRC) cells. However, inhibition of autophagy using a small molecular inhibitor 3-methyladenine (3-MA) and ATG5 siRNA did not increase SN-38-induced cytotoxicity in CRC cells. Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53. Subsequently, we identified a potential mechanism of this cooperative interaction by showing that CQ and SN-38 acted together to trigger reactive oxygen species (ROS) burst, upregulate p53 expression, elicit the ...
Source: Free Radical Biology and Medicine - January 24, 2017 Category: Biology Authors: Chen P, Luo X, Nie P, Wu B, Xu W, Shi X, Chang H, Li B, Yu X, Zou Z Tags: Free Radic Biol Med Source Type: research