کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8321912 | 1539840 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endothelial replicative senescence delayed by the inhibition of MTORC1 signaling involves MicroRNA-107
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ECMeIF4E binding protein 1cyclin dependent kinase 6RPS64EBP1S6K1S6 kinase 1HUVECUTRmTORSDSBSA - BSACdk6 - cdk6bovine serum albumin - آلبومین سرم گاوRISC - خطرRapamycin - راپامایسینsodium dodecyl sulfate - سدیم دودسیل سولفاتHuman endothelial cell - سلول اندوتلیال انسانیHuman umbilical vein endothelial cell - سلول اندوتلیالی ورید ناقل انسانیphosphatase and tensin homolog - فسفاتاز و تنسین همولوگRNA-Induced Silencing Complex - مجتمع خاموش کننده RNA inducedendothelial cell medium - محیط سلول اندوتلیالUn-translated region - منطقه غیر ترجمهMicroRNA - میکرو RNA MiRNA - میکروRNA، ریزآرانای، miRNAmammalian target of rapamycin - هدف پستانداران رپامایسینRibosomal protein S6 - پروتئین Ribosomal S6Cellular senescence - پیری سلولیPten - ژن PTEN
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Endothelial replicative senescence delayed by the inhibition of MTORC1 signaling involves MicroRNA-107 Endothelial replicative senescence delayed by the inhibition of MTORC1 signaling involves MicroRNA-107](/preview/png/8321912.png)
چکیده انگلیسی
Accumulation of senescent endothelial cells can contribute to endothelium dysfunction. Suppression of MTOR signaling has been shown to delay senescence but the mechanism that underpins this effect, particularly one that involves miRNAs, remains to be further defined. This study sought to identify miRNAs involved in MTORC1-mediated inhibition of replicative senescence in endothelial cells. Pre-senescent HUVECs were prolonged treated with low dose rapamycin (1â¯nM), an MTOR inhibitor. Rapamycin treatment down-regulated the phosphorylated MTOR, RPS6 and 4EBP1 expressions, which confirmed MTORC1 suppression. Prolonged low dose rapamycin treatment has significantly reduced the percentage of senescence-associated beta galactosidase (SA-β gal) positively stained senescent cells and P16INK4A expression in these cells. On the contrary, the percentage of BrdU-labelled proliferating cells has significantly increased. RPTOR, a positive regulator of MTORC1 was knockdown using RPTOR siRNA to inhibit MTORC1 activation. RPTOR knockdown was evidenced by significant suppressions of RPTOR mRNA and protein expression levels. In these cells, the expression of miR-107 was down-regulated whereas miR-145-5p and miR-217 were up-regulated. Target gene prediction revealed PTEN as the target of miR-107 and this was confirmed by biotin pull-down assay. Over-expression of miR-107 has decreased PTEN expression, increased MTORC1 activity, induced cell cycle arrest at G0/G1 phase and up-regulated P16INK4A expression but mitigated tube formation. Collectively, our findings revealed that delayed endothelial replicative senescence caused by the inhibition of MTORC1 activation could be modulated by miR-107 via its influence on PTEN.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 101, August 2018, Pages 64-73
Journal: The International Journal of Biochemistry & Cell Biology - Volume 101, August 2018, Pages 64-73
نویسندگان
Eng-Soon Khor, Pooi-Fong Wong,