Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway.
Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway.
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晚期糖基化终产物通过RAGE/PI3K/AKT/mTOR途径触发心肌细胞自噬。
DOI：
10.1186/1475-2840-13-78
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发表时间：
2014-04-14
影响因子：
9.3
通讯作者：
Wang N
中科院分区：
文献类型：
--
作者：
Hou X;Hu Z;Xu H;Xu J;Zhang S;Zhong Y;He X;Wang N
体外培养乳鼠心肌细胞，用不同浓度的AGEs处理。Western blot检测两种经典的自噬标志物微管相关蛋白1轻链3（LC 3）和Beclin-1。分别对细胞施加对Akt和磷脂酰肌醇3-磷酸激酶（PI 3 K）/Akt/mTOR通路的抑制。AGEs处理后，Beclin-1和LC 3 II的表达增强，自噬空泡数量增加，细胞活力降低，且呈剂量依赖性。AGEs还可通过抑制PI 3 K/Akt/mTOR通路。抑制Beclin-1和LC 3 II/I的表达，抑制细胞自噬，伴随着培养细胞中PI 3 K/Akt/mTOR通路的重新激活。值得注意的是，PI 3 K/Akt/mTOR通路的抑制的存在消除了抑制对心肌细胞的保护作用。这项研究提供的证据表明，AGEs诱导心肌细胞自噬，至少部分，通过抑制PI 3 K/Akt/mTOR途径，通过ATP酶。以往的研究表明，晚期糖基化终产物（AGEs）的积累可诱导心肌细胞凋亡，导致心脏功能障碍。然而，AGEs对心肌细胞中另一种细胞死亡途径自噬的影响仍然未知。
Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively. AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes. This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE. Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown.
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影响因子：
13.3
作者：
Saiki, Shinji;Sasazawa, Yukiko;Hattori, Nobutaka
通讯作者：
Hattori, Nobutaka
DOI：
10.1253/circj.cj-08-0669
发表时间：
2008-01-01
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Nishida, Kazuhiko;Otsu, Kinya
通讯作者：
Otsu, Kinya
影响因子：
10.8
作者：
Knaapen, MWM;Davies, MJ;Kockx, MM
通讯作者：
Kockx, MM
ERK 和 Akt 信号通路参与大鼠血管平滑肌细胞晚期糖基化终产物诱导的自噬
影响因子：
5.4
作者：
Hu P;Lai D;Lu P;Gao J;He H
通讯作者：
He H
影响因子：
9.3
作者：
Qin Q;Niu J;Wang Z;Xu W;Qiao Z;Gu Y
通讯作者：
Gu Y