کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4327868 | 1614143 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evidence that the major metabolites accumulating in medium-chain acyl-CoA dehydrogenase deficiency disturb mitochondrial energy homeostasis in rat brain
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کلمات کلیدی
HEPESEGTAANTCCCPATCBSA - BSAatractyloside - آتراتکتیلوزیدbovine serum albumine - آلبومین سرم گاوethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid - اتیلن گلیکول بیست (2-aminoethylether) -N، N، N '، N'-tetraacetic acidDecanoic acid - اسید Decanoicadenine nucleotide translocator - ترجمه آدنین نوکلئوتیدیcarbonyl cyanide m-chlorophenyl hydrazone - کربونیل سیانید m-کلروفنیل هیدرازون
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an inherited metabolic disorder of fatty acid oxidation in which the affected patients predominantly present high levels of octanoic (OA) and decanoic (DA) acids and their glycine and carnitine by-products in tissues and body fluids. It is clinically characterized by episodic encephalopathic crises with coma and seizures, as well as by progressive neurological involvement, whose pathophysiology is poorly known. In the present work, we investigated the in vitro effects of OA and DA on various parameters of energy homeostasis in mitochondrial preparations from brain of young rats. We found that OA and DA markedly increased state 4 respiration and diminished state 3 respiration as well as the respiratory control ratio, the mitochondrial membrane potential and the matrix NAD(P)H levels. In addition, DA-elicited increase in oxygen consumption in state 4 respiration was partially prevented by atractyloside, indicating the involvement of the adenine nucleotide translocator. OA and DA also reduced ADP/O ratio, CCCP-stimulated respiration and the activities of respiratory chain complexes. The data indicate that the major accumulating fatty acids in MCADD act as uncouplers of oxidative phosphorylation and as metabolic inhibitors. Furthermore, DA, but not OA, provoked a marked mitochondrial swelling and cytochrome c release from mitochondria, reflecting a permeabilization of the inner mitochondrial membrane. Taken together, these data suggest that OA and DA impair brain mitochondrial energy homeostasis that could underlie at least in part the neuropathology of MCADD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1296, 16 October 2009, Pages 117-126
Journal: Brain Research - Volume 1296, 16 October 2009, Pages 117-126
نویسندگان
PatrÃcia Fernanda Schuck, Gustavo da Costa Ferreira, Anelise Miotti Tonin, Carolina Maso Viegas, Estela Natacha Brandt Busanello, Alana Pimentel Moura, Ãngela Zanatta, Fábio Klamt, Moacir Wajner,