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
![عکس صفحه اول مقاله: Inhibition of mTOR improves the impairment of acidification in autophagic vesicles caused by hepatic steatosis Inhibition of mTOR improves the impairment of acidification in autophagic vesicles caused by hepatic steatosis](/preview/png/10749592.png)
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,