Antioxidants & redox signaling
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Antioxid. Redox Signal. · Dec 2013
Antioxidant activity of sestrin 2 controls neuropathic pain after peripheral nerve injury.
Neuropathic pain is a chronic debilitating disease that is often unresponsive to currently available treatments. Emerging lines of evidence indicate that reactive oxygen species (ROS) are required for the development and maintenance of neuropathic pain. However, little is known about endogenous mechanisms that neutralize the pain-relevant effects of ROS. In the present study, we tested whether the stress-responsive antioxidant protein Sestrin 2 (Sesn2) blocks the ROS-induced neuropathic pain processing in vivo. ⋯ Sesn2 controls ROS-dependent neuropathic pain signaling after peripheral nerve injury and may, thus, provide a potential new target for the clinical management of chronic neuropathic pain conditions.
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Antioxid. Redox Signal. · Dec 2013
A novel antihypoglycemic role of inducible nitric oxide synthase in liver inflammatory response induced by dietary cholesterol and endotoxemia.
The current study aim was to elucidate the antihypoglycemic role and mechanism of inducible nitric oxide synthase (iNOS) under inflammatory stress. ⋯ These data highlight the essential role of iNOS in the glycemic response to LPS in NASH conditions and argues for the beneficial effects of iNOS.
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Antioxid. Redox Signal. · Nov 2013
SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex.
SirT1 is a class III histone deacetylase that has been implicated in metabolic and reactive oxygen species control. In the vasculature it has been shown to decrease endothelial superoxide production, prevent endothelial dysfunction and atherosclerosis. However, the mechanisms that mediate SirT1 antioxidant functions remain to be characterized. The transcription factor FoxO3a and the transcriptional coactivator peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α) have been shown to induce the expression of antioxidant genes and to be deacetylated by SirT1. ⋯ We show that SirT1 regulation of antioxidant genes in vascular endothelial cells depends on the formation of a FoxO3a/PGC-1α complex.
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Antioxid. Redox Signal. · Oct 2013
HNO enhances SERCA2a activity and cardiomyocyte function by promoting redox-dependent phospholamban oligomerization.
Nitroxyl (HNO) interacts with thiols to act as a redox-sensitive modulator of protein function. It enhances sarcoplasmic reticular Ca(2+) uptake and myofilament Ca(2+) sensitivity, improving cardiac contractility. This activity has led to clinical testing of HNO donors for heart failure. Here we tested whether HNO alters the inhibitory interaction between phospholamban (PLN) and the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in a redox-dependent manner, improving Ca(2+) handling in isolated myocytes/hearts. ⋯ PLN plays a central role in HNO-induced enhancement of SERCA2a activity, leading to increased inotropy/lusitropy in intact myocytes and hearts. PLN remains physically associated with SERCA2a; however, less monomeric PLN is available resulting in decreased inhibition of the enzyme. These findings offer new avenues to improve Ca(2+) handling in failing hearts.
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Antioxid. Redox Signal. · Aug 2013
Ferric Iron and Cobalt (III) compounds to safely decrease hydrogen sulfide in the body?
To sort out the putative roles of endogenous hydrogen sulfide (H2S) in clinical conditions wherein systemic inflammation or hypoxia is present, it becomes crucial to develop approaches capable of affecting H2S concentration that can be safely applied in humans. We have investigated a paradigm, which could achieve such a goal, using vitamin B12 (vit. B12), at the dose recommended in cyanide poisoning, and very low levels of methemoglobin (MetHb). ⋯ Three to five percent MetHb prevented H2S induced hyperventilation in vivo and decreased exogenous H2S in vitro by 25-40 μM within 30 s. Our observations lead to the hypothesis that innocuous levels of MetHb and vit. B12 could be a used as an effective and safe way to test the role of endogenous H2S in vivo.