کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8324488 | 1539910 | 2013 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Up-regulation of 2-oxoglutarate dehydrogenase as a stress response
ترجمه فارسی عنوان
تنظیم مقادیر 2-اگزئوگلوترات دهیدروژناز به عنوان پاسخ استرس
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
یون منگنز، سمیت اتانول، انتقال عصبی گلوتامات، 2-اگزوکلوترات دهیدروژناز، پاسخ استرس،
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
2-Oxoglutarate dehydrogenase multienzyme complex (OGDHC) operates at a metabolic cross-road, mediating Ca2+- and ADP-dependent signals in mitochondria. Here, we test our hypothesis that OGDHC plays a major role in the neurotransmitter metabolism and associated stress response. This possibility was assessed using succinyl phosphonate (SP), a highly specific and efficient in vivo inhibitor of OGDHC. Animals exposed to toxicants (SP, ethanol or MnCl2), trauma or acute hypoxia showed intrinsic up-regulation of OGDHC in brain and heart. The known mechanism of the SP action as OGDHC inhibitor pointed to the up-regulation triggered by the enzyme impairment. The animal behavior and skeletal muscle or heart performance were tested to correlate physiology with the OGDHC regulation and associated changes in the glutamate and cellular energy status. The SP-treated animals exhibited interdependent changes in the brain OGDHC activity, glutamate level and cardiac autonomic balance, suggesting the neurotransmitter role of glutamate to be involved in the changed heart performance. Energy insufficiency after OGDHC inhibition was detectable neither in animals up to 25Â mg/kg SP, nor in cell culture during 24Â h incubation with 0.1Â mM SP. However, in animals subjected to acute ethanol intoxication SP did evoke energy deficit, decreasing muscular strength and locomotion and increasing the narcotic sleep duration. This correlated with the SP-induced decrease in NAD(P)H levels of the ethanol-exposed neurons. Thus, we show the existence of natural mechanisms to up-regulate mammalian OGDHC in response to stress, with both the glutamate neurotransmission and energy production potentially involved in the OGDHC impact on physiological performance.This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 1, January 2013, Pages 175-189
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 1, January 2013, Pages 175-189
نویسندگان
Anastasia Graf, Lidia Trofimova, Alexandra Loshinskaja, Garik Mkrtchyan, Anastasiia Strokina, Maxim Lovat, Adam Tylicky, Slawomir Strumilo, Lucien Bettendorff, Victoria I. Bunik,