کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10739343 | 1046872 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacogenomic profiling of an oxidative stress-mediated spongiform encephalopathy
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کلمات کلیدی
FDRCatalytic antioxidantAkt1SOD2qPCRMicroarrayscDNA - cDNAComplementary DNA - DNA تکمیلیOxidative stress - تنش اکسیداتیوNeurodegeneration - تولید نوروژنیکFree radicals - رادیکال آزادSuperoxide - سوپر اکسیدSuperoxide dismutase - سوکسوکس دیسموتازMouse models - مدل موشgene expression profiling - مشخصات ژن بیانquantitative polymerase chain reaction - واکنش زنجیره ای پلیمراز کمیprotein kinase B - پروتئین کیناز B
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
The majority of cellular superoxide is generated in the mitochondria as a by-product of normal oxidative metabolism. In the mitochondria, superoxide is detoxified by manganese superoxide dismutase (SOD2). Mice lacking SOD2 demonstrate a multifaceted neonatal lethal phenotype, including a spongiform encephalopathy that is preventable through antioxidant treatment. The molecular events behind the observed pathology in the cortex of these mice are unknown. We hypothesized that the lack of SOD2 would result in significant changes in cortical gene expression and that therapeutically beneficial antioxidant treatment would normalize the expression of some genes, providing insight into the mechanism by which mitochondrial oxidative stress results in neurodegeneration. We report the identification of gene expression profiles associated with this paradigm, which characterize the degree of response to the pharmacologic intervention. We have identified specific pathways targeted by endogenous oxidative stress, including glutathione metabolism, iron metabolism, and cell-survival pathways centering on the kinase AKT. The normalization of expression of some of these pathways by antioxidant treatment suggests approaches to treating disease in which endogenous oxidative stress plays a role.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 39, Issue 2, 15 July 2005, Pages 152-163
Journal: Free Radical Biology and Medicine - Volume 39, Issue 2, 15 July 2005, Pages 152-163
نویسندگان
Tamara R. Golden, Alan Hubbard, Karl J. Morten, Doug Hinerfeld, Simon Melov,