کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8298729 | 1537041 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Uncoupling, metabolic inhibition and induction of mitochondrial permeability transition in rat liver mitochondria caused by the major long-chain hydroxyl monocarboxylic fatty acids accumulating in LCHAD deficiency
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کلمات کلیدی
MPTN-[2-hydroxyethyl]piperazine-N′-[2-ethane-sulfonic acid]fluorescence arbitrary unitsethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acidcarbonyl cyanide 3-chlorophenyl hydrazineLCHADALMATCCCCPRCRΔΨmANTLCFAN-ethylmaleimideEGTAFAUDTTHEPESEtOHAlamethicin - AlamethicBSA - BSAatractyloside - آتراتکتیلوزیدbovine serum albumin - آلبومین سرم گاوEthanol - اتانولLong-chain fatty acids - اسیدهای چرب بلند زنجیره ایmitochondrial permeability transition - انتقال نفوذپذیری میتوکندریCSA - ایالات مؤتلفهٔ آمریکاadenine nucleotide translocator - ترجمه آدنین نوکلئوتیدیGDP - تولید ناخالص ملیdithiothreitol - دیتیوتریتولruthenium red - رتنیم قرمزcyclosporin A - سیکلوسپورین Arespiratory control ratio - نسبت کنترل تنفسیNEM - نهMitochondrial membrane potential - پتانسیل غشای میتوکندریCalcium - کلسیمguanosine diphosphate - گوانوزین دی فسفات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش گیاه شناسی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Patients with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency commonly present liver dysfunction whose pathogenesis is unknown. We studied the effects of long-chain 3-hydroxylated fatty acids (LCHFA) that accumulate in LCHAD deficiency on liver bioenergetics using mitochondrial preparations from young rats. We provide strong evidence that 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, the monocarboxylic acids that are found at the highest tissue concentrations in this disorder, act as metabolic inhibitors and uncouplers of oxidative phosphorylation. These conclusions are based on the findings that these fatty acids decreased ADP-stimulated (state 3) and uncoupled respiration, mitochondrial membrane potential and NAD(P)H content, and, in contrast, increased resting (state 4) respiration. We also verified that 3HTA and 3HPA markedly reduced Ca2Â + retention capacity and induced swelling in Ca2Â +-loaded mitochondria. These effects were mediated by mitochondrial permeability transition (MPT) induction since they were totally prevented by the classical MPT inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca2Â + uptake blocker. Taken together, our data demonstrate that the major monocarboxylic LCHFA accumulating in LCHAD deficiency disrupt energy mitochondrial homeostasis in the liver. It is proposed that this pathomechanism may explain at least in part the hepatic alterations characteristic of the affected patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1847, Issues 6â7, JuneâJuly 2015, Pages 620-628
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1847, Issues 6â7, JuneâJuly 2015, Pages 620-628
نویسندگان
Fernanda Hermes Hickmann, Cristiane Cecatto, Daniele Kleemann, Wagner Oliveira Monteiro, Roger Frigério Castilho, Alexandre Umpierrez Amaral, Moacir Wajner,