کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5846485 | 1128482 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers
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کلمات کلیدی
Cbztetramethylrhodamine methylesterFDATMRMMPTKRHIP3LC3ATGHepatocytes - hepatocytesI/R - I / Rinositol-1,4,5-triphosphate - inositol-1،4،5-triphosphateAutophagy - اتوفاژیFood & Drug Administration - اداره غذا و دارویmitochondrial permeability transition - انتقال نفوذپذیری میتوکندریischemia/reperfusion - ایسکمی / رپرفیوژنMitochondria - میتوکندریاmicrotubule-associated protein 1 light chain 3 - پروتئین مرتبط با میکروتوبول 1 زنجیره سبک 3Autophagy-related proteins - پروتئین های مربوط به AutophagyPropidium iodide - پروتئین یدیدcarbamazepine - کاربامازپینChloroquine - کلروکین Calcium - کلسیم
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 273, Issue 3, 15 December 2013, Pages 600-610
Journal: Toxicology and Applied Pharmacology - Volume 273, Issue 3, 15 December 2013, Pages 600-610
نویسندگان
Jae-Sung Kim, Jin-Hee Wang, Thomas G. Biel, Do-Sung Kim, Joseph A. Flores-Toro, Richa Vijayvargiya, Ivan Zendejas, Kevin E. Behrns,