کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245925 | 1209958 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
GSHCYP2E1MTPDCFDAHFCTMRMNACtBOOHzVAD-fmkTNFMFCSDSDMEMtetramethylrhodamine methylester7-hydroxy-4-trifluoromethylcoumarin - 7 هیدروکسی 4-تری فلووریمتیکومارینDulbecco’s modified Eagle medium - Modified Eagle اصلاح شده DulbeccoN-acetylcysteine - N-استیل سیستئینROS - ROSΔψ - Δρmitochondrial permeability transition - انتقال نفوذپذیری میتوکندریsodium dodecyl sulfate - سدیم دودسیل سولفاتcytochrome P450 2E1 - سیتوکروم P450 2E1endoplasmic reticulum - شبکه آندوپلاسمی tumor necrosis factor - فاکتور نکروز تومورTertiary butyl hydroperoxide - هیدروپراکسید استیل بوتیلMitochondrial membrane potential - پتانسیل غشای میتوکندریreduced glutathione - کاهش گلوتاتیونReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells](/preview/png/9245925.png)
چکیده انگلیسی
Background & Aims: Alcohol consumption exacerbates liver injury in chronic hepatitis C, and enhanced mitochondrial oxidative stress is one possible mechanism. The aim of this study was to determine whether hepatitis C virus core protein and alcohol-inducible cytochrome P450 2E1 contribute to reactive oxygen species production and cytotoxicity in human hepatoma cells. Methods: Huh-7 cells expressing core protein, cytochrome P450 2E1, or both were exposed to 0.1 mmol/L tertiary butyl hydroperoxide, tumor necrosis factor α, and/or 25 mmol/L ethanol. Cytotoxicity, reactive oxygen species production, glutathione content, and mitochondrial membrane potential were measured. Results: Expression of core/cytochrome P450 2E1 synergistically enhanced cell death induced by either tertiary butyl hydroperoxide or tumor necrosis factor α. After tertiary butyl hydroperoxide treatment, total reactive oxygen species production was increased more than 3-fold compared with cells that did not express core and cytochrome P450 2E1. Mitochondrial depolarization and reduced glutathione depletion occurred as well, and cell death was prevented by inhibition of mitochondrial permeability transition or caspase activity. Confocal microscopy showed that the mitochondria themselves were the origin of the reactive oxygen species. In the absence of core/cytochrome P450 2E1 expression, mitochondrial changes and cell death did not occur. Ethanol treatment further decreased mitochondrial reduced glutathione content and exacerbated mitochondrial reactive oxygen species production, depolarization, and cell death. All these effects were prevented by the antioxidant N-acetylcysteine. Conclusions: Mitochondrial reactive oxygen species production is induced by hepatitis C virus core and cytochrome P450 2E1, resulting in a reduction of mitochondrial antioxidant capacity and sensitivity to oxidants and tumor necrosis factor α. Alcohol further depletes mitochondrial reduced glutathione, which exacerbates depolarization and cell death. Sensitization of mitochondria to oxidative insults is thus a potential mechanism for alcohol-related exacerbation of liver injury in chronic hepatitis C.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 128, Issue 1, January 2005, Pages 96-107
Journal: Gastroenterology - Volume 128, Issue 1, January 2005, Pages 96-107
نویسندگان
Kazuhiro Otani, Masaaki Korenaga, Michael R. Beard, Kui Li, Ting Qian, Lori A. Showalter, Aman K. Singh, Ting Wang, Steven A. Weinman,