کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911706 1046829 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production
چکیده انگلیسی

Pharmacological mitochondrial ATP-sensitive K+ channel (mitoKATP) opening protects against ischemic damage and mimics ischemic preconditioning. However, physiological and pathological signaling events that open this channel are still not fully understood. We found that catalase, which removes H2O2, is capable of reversing the beneficial effects of ischemic preconditioning but not of mitoKATP agonist diazoxide. On the other hand, 2-mercaptopropionylglycine prevented cardioprotection in both cases, suggesting that this compound may present effects other than scavenging of reactive oxygen species. Indeed, 2-mercaptopropionylglycine and a second thiol-reducing agent, dithiothreitol, impair diazoxide-mediated activation of mitoKATP in isolated heart mitochondria. This demonstrates that mitoKATP activity is regulated by thiol redox status. Furthermore, stimulating the generation of endogenous mitochondrial reactive oxygen species or treating samples with H2O2 strongly enhances mitoKATP activity, in a manner probably dependent on redox sensors located in the channel's sulfonylurea receptor. We also demonstrate that mitoKATP channel activity effectively prevents mitochondrial reactive oxygen release. Collectively, our results suggest that mitoKATP acts as a reactive oxygen sensor that decreases mitochondrial free radical generation in response to enhanced local levels of oxidants. As a result, these channels regulate mitochondrial redox state under physiological conditions and prevent oxidative stress under pathological conditions such as ischemia/reperfusion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 42, Issue 7, 1 April 2007, Pages 1039–1048
نویسندگان
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