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Source: Free Radical Biology and Medicine

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Total 199 results found since Jan 2013.

Glutathione-S-transferase omega 1 (GSTO1-1) acts as mediator of signaling pathways involved in aflatoxin B1-induced apoptosis-autophagy crosstalk in macrophages.
Abstract Aflatoxin B1 (AFB1) is the most toxic aflatoxin species and has been shown to be associated with specific as well as non-specific immune responses. In the present study, using murine macrophage Raw 264.7 cells as a model, we report that short exposure (6h) to AFB1 caused an increase in the cellular calcium pool in mitochondria, which in turn elevated reactive oxygen species (ROS)-mediated oxidative stress and led to loss of mitochondrial membrane potential and ultimately c-Jun N-terminal kinases (JNK)-mediated caspase-dependent cell death. On the contrary, longer exposure (12h) to AFB1 reduced JNK phospho...
Source: Free Radical Biology and Medicine - November 9, 2015 Category: Biology Authors: Paul S, Jakhar R, Bhardwaj M, Kang SC Tags: Free Radic Biol Med Source Type: research

Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase.
Abstract Peroxiredoxin-3 (Prx3) accounts for about 90% of mitochondrial peroxidase activity, and its marked upregulation in many cancers is important for cell survival. Prx3 oxidation can critically alter peroxide signaling and defense and can be a seminal event in promoting cell death. Here it is shown that this mechanism can be exploited pharmacologically by combinations of clinically available drugs that compromise Prx3 function in different ways. Clinically relevant levels of the thiosemicarbazone iron chelators triapine (Tp) and 2,2'-Dipyridyl-N,N-dimethylsemicarbazone (Dp44mT) promote selective oxidation of ...
Source: Free Radical Biology and Medicine - December 11, 2015 Category: Biology Authors: Myers CR Tags: Free Radic Biol Med Source Type: research

Down-regulation of the mitochondrial matrix peptidase ClpP in muscle cells causes mitochondrial dysfunction and decreases cell proliferation.
Abstract The caseinolytic peptidase P (ClpP) is the endopeptidase component of the mitochondrial matrix ATP-dependent ClpXP protease. ClpP degrades unfolded proteins to maintain mitochondrial protein homeostasis and is involved in the initiation of the mitochondrial unfolded protein response (UPR(mt)). Outside of an integral role in the UPR(mt), the cellular function of ClpP is not well characterized in mammalian cells. To investigate the role of ClpP in mitochondrial function, we generated C2C12 muscle cells that are deficient in ClpP using siRNA or stable knockdown using lentiviral transduction. Reduction of Clp...
Source: Free Radical Biology and Medicine - December 23, 2015 Category: Biology Authors: Deepa SS, Bhaskaran S, Ranjit R, Qaisar R, Nair BC, Liu Y, Walsh ME, Fok WC, Van Remmen H Tags: Free Radic Biol Med Source Type: research

Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system.
In conclusion, we demonstrated that CA prevented APAP-induced hepatotoxicity by decreasing Keap1 expression, inhibiting binding of Keap1 to Nrf2, and thus activating Nrf2 and leading to increased expression of antioxidative signals including HO-1 and NQO1. PMID: 26721592 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - December 23, 2015 Category: Biology Authors: Pang C, Zheng Z, Shi L, Sheng Y, Wei H, Wang Z, Ji L Tags: Free Radic Biol Med Source Type: research

The neutral Sphingomyelinase-2 is involved in angiogenic signaling triggered by oxidized LDL.
In conclusion, low oxLDL concentration triggers sprouting angiogenesis that involves ROS-induced activation of the neutral sphingomyelinase-2/sphingosine kinase-1 pathway, and is effectively inhibited by GW4869. PMID: 26855418 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - February 4, 2016 Category: Biology Authors: Camaré C, Augé N, Pucelle M, Saint-Lebes B, Grazide MH, Nègre-Salvayre A, Salvayre R Tags: Free Radic Biol Med Source Type: research

NADPH oxidase 4 contributes to connective tissue growth factor expression through Smad3-dependent signaling pathway.
Abstract Transforming growth factor-β (TGF-β)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-β/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro. NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-β1-induced CTGF expression and ROS gene...
Source: Free Radical Biology and Medicine - March 2, 2016 Category: Biology Authors: Liu XH, Zhang QY, Pan LL, Liu SY, Xu P, Luo XL, Zou SL, Xin H, Qu LF, Zhu YZ Tags: Free Radic Biol Med Source Type: research

Electrophilic nitro-fatty acids prevent astrocyte-mediated toxicity to motor neurons in a cell model of familial amyotrophic lateral sclerosis via nuclear factor erythroid 2-related factor activation.
Abstract Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons associated to an inflammatory process that usually aggravates the disease progression. In ALS animal models, the activation of the transcription factor Nrf2 in astrocytes confers protection to neighboring neurons. It is...
Source: Free Radical Biology and Medicine - March 20, 2016 Category: Biology Authors: Diaz-Amarilla P, Miquel E, Trostchansky A, Trias E, Ferreira AM, Freeman BA, Cassina P, Barbeito L, Vargas MR, Rubbo H Tags: Free Radic Biol Med Source Type: research

Liraglutide protects cardiac microvascular endothelial cells against hypoxia/reoxygenation injury through the suppression of the SR-Ca(2+)-XO-ROS axis via activation of the GLP-1R/PI3K/Akt/Survivin pathways.
Abstract Microvascular endothelial cells (CMECs) oxidative damage resulting from hypoxia/reoxygenation (H/R) injury is responsible for microcirculation perfusion disturbances and the progression of cardiac dysfunction. However, few strategies are available to reverse such pathologies. Here, we studied the effects and mechanisms of liraglutide on CEMCs oxidative damage, focusing in particular on calcium overload-triggered free radical injury signals and the GLP-1R/PI3K/Akt/Survivin survival pathways. The results indicate that H/R increased IP3R expression but reduced SERCA2a expression, which rapidly raised intrace...
Source: Free Radical Biology and Medicine - March 29, 2016 Category: Biology Authors: Zhang Y, Zhou H, Wu W, Shi C, Hu S, Yin T, Ma Q, Han T, Zhang Y, Tian F, Chen Y Tags: Free Radic Biol Med Source Type: research

Activation of Wnt/β-catenin Signaling by Hydrogen Peroxide Transcriptionally Inhibits NaV1.5 Expression.
Abstract Oxidants and canonical Wnt/β-catenin signaling have been shown to decrease cardiac Na(+) channel activity by suppressing NaV1.5 expression. Our aims are to determine if hydrogen peroxide (H2O2), one oxidant of reactive oxygen species (ROS), activates Wnt/β-catenin signaling and promotes β-catenin nuclear activity, leading to suppression of NaV1.5 expression and if this suppression requires the interaction of β-catenin with its nuclear partner, TCF4 (also called TCF7L2) to decrease SCN5a promoter activity. The results demonstrated that H2O2 increased β-catenin, but not TCF4 nuclear localization determ...
Source: Free Radical Biology and Medicine - April 7, 2016 Category: Biology Authors: Wang N, Huo R, Cai B, Lu Y, Ye B, Li X, Li F, Xu H Tags: Free Radic Biol Med Source Type: research

SVCT2, a potential therapeutic target, protects against oxidative stress during ethanol-induced neurotoxicity via JNK/p38 MAPKs, NF-κB and miRNA125a-5p.
Abstract Sodium vitamin C transporter 2 (SVCT2) plays a key role in transporting ascorbic acid (AA), an important intracellular antioxidant, into neurons. It is well known that ethanol (EtOH) abuse causes significant neurodegeneration, as well as endogenous AA release in certain encephalic regions. Here, we identified that SVCT2 forms part of a self-defense mechanism that protects against oxidative stress in binge drinking rats, and SVCT2 levels are correlated with antioxidants and neuronal injury. Four days of binge drinking led to massive neuron degeneration in prefrontal cortex (PFC), accompanied by increased l...
Source: Free Radical Biology and Medicine - April 12, 2016 Category: Biology Authors: Tian H, Ye X, Hou X, Yang X, Yang J, Wu C Tags: Free Radic Biol Med Source Type: research

β-Lapachone increases phase II antioxidant enzyme expression via NQO1-AMPK/PI3K-Nrf2/ARE signaling in rat primary astrocytes.
Abstract β-Lapachone (β-LAP) is a naturally occurring quinine that exerts a number of pharmacological actions including antibacterial, antifungal, antimalarial, and antitumor activities. In the present study, we investigated whether β-LAP has an antioxidant effect in rat primary astrocytes. β-LAP suppressed intracellular reactive oxygen species (ROS) production induced by hydrogen peroxide and inhibited astroglial cell death. It also increased astrocytic expression of phase II antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), manganese superoxide dismutase (MnSOD), a...
Source: Free Radical Biology and Medicine - May 26, 2016 Category: Biology Authors: Park JS, Lee YY, Kim J, Seo H, Kim HS Tags: Free Radic Biol Med Source Type: research

Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress by Vitamin D in Endothelial Cells.
Abstract Endoplasmic reticulum (ER) stress and oxidative stress promote endothelial dysfunction and atherosclerosis. Since vitamin D has been shown in several studies to lower the risk of cardiovascular disease, we examined the effects of vitamin D on ER stress and oxidative stress in endothelial cells. ER stress was measured using the placental secreted alkaline phosphatase assay and oxidative stress was measured by hydroethidine fluorescence. Expression of ER stress markers, including glucose-regulated protein 78, c-jun N-terminal kinase 1 phosphorylation, and eukaryotic initiation factor 2α phosphorylation, as...
Source: Free Radical Biology and Medicine - July 21, 2016 Category: Biology Authors: Haas MJ, Jafri M, Wehmeier KR, Onstead-Haas LM, Mooradian AD Tags: Free Radic Biol Med Source Type: research

LRRC8A channels support TNF α-induced superoxide production by Nox1 which is required for receptor endocytosis.
LRRC8A channels support TNFα-induced superoxide production by Nox1 which is required for receptor endocytosis. Free Radic Biol Med. 2016 Nov 9;: Authors: Choi H, Ettinger N, Rohrbough J, Dikalova A, Nguyen HN, Lamb FS Abstract Leucine Rich Repeat Containing 8A (LRRC8A) is a required component of volume-regulated anion channels (VRACs). In vascular smooth muscle cells, tumor necrosis factor-α (TNFα) activates VRAC via type 1 TNFα receptors (TNFR1), and this requires superoxide (O2(•-)) production by NADPH oxidase 1 (Nox1). VRAC inhibitors suppress the inflammatory response to TNFα by an unknown ...
Source: Free Radical Biology and Medicine - November 8, 2016 Category: Biology Authors: Choi H, Ettinger N, Rohrbough J, Dikalova A, Nguyen HN, Lamb FS Tags: Free Radic Biol Med Source Type: research

Srb1 as a new redox target of cigarette smoke in human sebocytes.
In conclusion, exposure to CS, induced SRB1 post-translational modifications in sebocytes and this might affect sebocytes/skin functionality. PMID: 27865981 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - November 15, 2016 Category: Biology Authors: Crivellari I, Sticozzi C, Belmonte G, Muresan XM, Cervellati F, Pecorelli A, Cavicchio C, Maioli E, Zouboulis CC, Benedusi M, Cervellati C, Valacchi G Tags: Free Radic Biol Med Source Type: research

Intact mitochondrial Ca(2+) uniport is essential for agonist-induced activation of endothelial nitric oxide synthase (eNOS).
The objective of this study was to verify whether or not mitochondrial Ca(2+) uptake influences Ca(2+)-triggered NO(•) generation by endothelial NO(•) synthase (eNOS) in an immortalized endothelial cell line (EA.hy926), respective primary human umbilical vein endothelial cells (HUVECs) and eNOS-RFP (red fluorescent protein) expressing human embryonic kidney (HEK293) cells. We used novel genetically encoded fluorescent NO(•) probes, the geNOps, and Ca(2+) sensors to monitor single cell NO(•) and Ca(2+) dynamics upon cell treatment with ATP, an inositol 1,4,5-trisphosphate (IP3)-generating agonist. Mitochondrial Ca(2...
Source: Free Radical Biology and Medicine - December 2, 2016 Category: Biology Authors: Charoensin S, Eroglu E, Opelt M, Bischof H, Madreiter-Sokolowski CT, Kirsch A, Depaoli MR, Frank S, Schrammel A, Mayer B, Waldeck-Weiermair M, Graier WF, Malli R Tags: Free Radic Biol Med Source Type: research