Cyclin-dependent kinase 5 contributes to endoplasmic reticulum stress induced podocyte apoptosis via promoting MEKK1 phosphorylation at Ser280 in diabetic nephropathy.
Cyclin-dependent kinase 5 contributes to endoplasmic reticulum stress induced podocyte apoptosis via promoting MEKK1 phosphorylation at Ser280 in diabetic nephropathy.
复制标题
在糖尿病肾病中，细胞周期蛋白依赖性激酶 5 通过促进 MEKK1 Ser280 磷酸化，促进内质网应激诱导的足细胞凋亡。
DOI：
10.1016/j.cellsig.2016.12.009
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Liu Wei
中科院分区：
文献类型：
--
作者：
Zhang Yue;Gao Xiang;Chen Shuanggang;Zhao Min;Chen Jing;Liu Rui;Cheng Shengyang;Qi Mengyuan;Wang Shuo;Liu Wei
据报道，内质网（ER）应激与糖尿病肾病足细胞凋亡相关，但 ER 信号在足细胞凋亡中的机制尚未完全阐明。我们前期的研究表明，细胞周期蛋白依赖性激酶5（Cdk5）与糖尿病肾病足细胞凋亡相关。本研究旨在探讨 Cdk5 活性是否以及如何在糖尿病肾病 ER 应激诱导的足细胞凋亡中发挥作用。结果表明，在高糖处理的足细胞中，除了诱导 Cdk5 和细胞凋亡外，GRP78 及其两个传感器以及 CHOP 和 cleaved caspase-12 也被诱导。经过处理的 salubrinal 可以减弱这些反应。 ER应激诱导剂衣霉素也随着GRP78的增加而上调足细胞中Cdk5的激酶活性和蛋白表达。另一方面，在衣霉素处理的足细胞中，Cdk5 在 Ser280 位点磷酸化 MEKK1，并且它们一起增加 JNK 磷酸化。此外，破坏该途径可以减少衣霉素诱导的足细胞凋亡。因此，我们的研究证明Cdk5可能在糖尿病肾病中ER应激通过MEKK1/JNK通路诱导足细胞凋亡中发挥重要作用。
Endoplasmic reticulum (ER) stress has been reported to be associated with podocyte apoptosis in diabetic nephropathy, but the mechanism of ER signaling in podocyte apoptosis hasn't been fully understood. Our previous studies have demonstrated that Cyclin-dependent kinase 5 (Cdk5) was associated with podocyte apoptosis in diabetic nephropathy. The present study was designed to examine whether and how Cdk5 activity plays a role in ER stress induced podocyte apoptosis in diabetic nephropathy. The results showed that along with induction of Cdk5 and apoptosis, GRP78 and its two sensors as well as CHOP and cleaved caspase-12 were induced in high glucose treated podocytes. These responses were attenuated by treated salubrinal. The ER stress inducer, tunicamycin, also up-regulated the kinase activity and protein expression of Cdk5 in podocytes accompanied with the increasing of GRP78. On the other hand, Cdk5 phosphorylates MEKK1 at Ser280 in tunicamycin treated podocytes, and together, they increase the JNK phosphorylation. Moreover, disruption of this pathway can decrease the podocyte apoptosis induced by tunicamycin. Therefore, our study proved that Cdk5 may play an important role in ER stress induced podocyte apoptosis through MEKK1/JNK pathway in diabetic nephropathy.
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DOI：
10.1016/j.mcn.2012.10.007
发表时间：
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期刊：
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影响因子：
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作者：
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