کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10749592 | 1050291 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of mTOR improves the impairment of acidification in autophagic vesicles caused by hepatic steatosis
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کلمات کلیدی
GFPLC3TBS-TmTORLTRTFEBPVDFLysoTracker Redvacuolar-ATPaseFBSNAFLDAutophagy - اتوفاژیnonalcoholic steatohepatitis - استاتو هپاتیت غیر الکلیSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدSodium dodecyl sulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اتیل آمید سدیم دودسیل سولفاتNonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceRapamycin - راپامایسینmicrotubule-associated protein light chain 3 - زنجیره سبک پروتئینی مرتبط با میکروتوبول 3fetal bovine serum - سرم جنین گاوendoplasmic reticulum - شبکه آندوپلاسمی Transcription factor EB - عامل رونویسی EBLysosome - لیزوزومNash - نوشmammalian target of rapamycin - هدف پستانداران رپامایسینgreen fluorescent protein - پروتئین فلورسنت سبزPolyvinylidene fluoride - پلی وینیلیدین فلوراید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The number of autophagic vesicles was increased in hepatocytes from obese KKAy mice as compared to control. Similarly, autophagic membrane protein LC3-II and lysosomal protein LAMP-2 expression were enhanced in KKAy mice liver. Nevertheless, both phospho-mTOR and p62 expression were augmented in KKAy mice liver. More than 70% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, the percentage of acidic autolysosomes was decreased in hepatocytes from KKAy mice significantly (40.1 ± 3.48%). Both protein and RNA level of V-ATPase subunits ATP6v1a, ATP6v1b, ATP6v1d in isolated lysosomes were suppressed in KKAy mice as compared to control. Interestingly, incubation with mTOR inhibitor rapamycin increased in the rate of LTR-positive autolysosomes in hepatocytes from KKAy mice and suppressed p62 accumulation in the liver from KKAy mice which correlated to an increase in the V-ATPase subunits expression. These results indicate that down-regulation of V-ATPase due to hepatic steatosis causes autophagic dysfunction via disruption of lysosomal and autophagic acidification. Moreover, activation of mTOR plays a pivotal role on dysregulation of lysosomal and autophagic acidification by modulation of V-ATPase expression and could therefore be a useful therapeutic target to ameliorate dysfunction of autophagy in NAFLD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 469, Issue 4, 22 January 2016, Pages 1104-1110
Journal: Biochemical and Biophysical Research Communications - Volume 469, Issue 4, 22 January 2016, Pages 1104-1110
نویسندگان
Eisuke Nakadera, Shunhei Yamashina, Kousuke Izumi, Yoshihiro Inami, Toshifumi Sato, Hirofumi Fukushima, Kazuyoshi Kon, Kenichi Ikejima, Takashi Ueno, Sumio Watanabe,