کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5904595 | 1158014 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Increasing leucine concentration stimulates mechanistic target of rapamycin signaling and cell growth in C2C12 skeletal muscle cells
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کلمات کلیدی
p70S6Keukaryotic initiation factor 4E-binding protein 1p70 S6 kinaseC2C12mTORC14E-BP1mTORFBSPCA - PCAAmino acids - اسید آمینه یا آمینو اسیدPerchloric acid - اسید پرکلریکanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of variancefetal bovine serum - سرم جنین گاوProtein synthesis - سنتز پروتئینSkeletal muscle - عضله اسکلتیMechanistic target of rapamycin - هدف مکانیکی رپامایسینmechanistic target of rapamycin complex 1 - هدف مکانیکی مجتمع رپامایسین 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
علوم غدد
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Leucine is a key amino acid for initiating translation in muscle cells, but the dose-dependent effects of leucine on intracellular signaling are poorly characterized. This study examined the effect that increasing doses of leucine would have on changes in mechanistic target of rapamycin (mTOR)-mediated signaling, rates of protein synthesis, and cell size in C2C12 cells. We hypothesized that a leucine “threshold” exists, which represents the minimum stimulus required to initiate mTOR signaling in muscle cells. Acute exposure to 1.5, 3.2, 5.0, and 16.1 mM leucine increased phosphorylation of mTORSer2448 (~1.4-fold; P < .04), 4E-BP1 Thr37/46 (~1.9-fold; P < .001), and rpS6Ser235/6 (~2.3-fold; P < .001). However, only p70S6kThr389 exhibited a dose-dependent response to leucine with all treatments higher than control (~4-fold; P < .001) and at least 5 mM higher than the 1.5-mM concentration (1.2-fold; P < .02). Rates of protein synthesis were not altered by any treatment. Seven days of exposure to 0.5, 1.5, 5.0, and 16.5 mM leucine resulted in an increase in cell size in at least 5 mM treatments (~1.6-fold, P < .001 vs control). Our findings indicate that even at low leucine concentrations, phosphorylation of proteins regulating translation initiation signaling is enhanced. The phosphorylation of p70S6kThr389 follows a leucine dose-response relationship, although this was not reflected by the acute protein synthetic response. Nevertheless, under the conditions of the present study, it appears that leucine concentrations of at least 5 mM are necessary to enhance cell growth.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nutrition Research - Volume 34, Issue 11, November 2014, Pages 1000-1007
Journal: Nutrition Research - Volume 34, Issue 11, November 2014, Pages 1000-1007
نویسندگان
José L. Areta, John A. Hawley, Ji-Ming Ye, M.H. Stanley Chan, Vernon G. Coffey,