کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1948126 1054675 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation
چکیده انگلیسی

BackgroundAtherosclerosis is one of the major complications of diabetes, which may result from insulin resistance via mitochondrial dysfunction. Although a strong association between insulin resistance and cardiovascular disease has been suggested, it is not clear yet whether stress-inducing factors damage mitochondria and insulin signaling pathway in cardiovascular tissues.MethodsWe investigated whether stress-induced mitochondrial dysfunction might alter the insulin/Akt signaling pathway in A10 rat vascular smooth muscle cells (VSMC).ResultsThe treatment of oxidized low density lipoprotein (oxLDL) decreased ATP contents, mitochondrial respiration activity, mRNA expressions of OXPHOS subunits and IRS-1/2 and insulin-mediated phosphorylations of Akt and AMP-activated protein kinase (AMPK). Similarly, dideoxycytidine (ddC), the mtDNA replication inhibitor, or rotenone, OXPHOS complex I inhibitor, inhibited the insulin-mediated pAkt while increased pAMPK regardless of insulin. Reciprocally, an inhibitor of Akt, triciribine (TCN), decreased cellular ATP contents. Overexpression of Akt dominant positive reversed the oxLDL- or ddC-mediated ATP decrease but AMPK activator did not. Akt activation also normalized the aberrant VSMC migration induced by ddC.ConclusionsDefective insulin signaling and mitochondrial function may collectively contribute to developing cardiovascular disease.General significanceAkt may be a possible therapeutic target for treating insulin resistance-associated atherosclerosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1800, Issue 3, March 2010, Pages 275–281
نویسندگان
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