Requirement of the phosphatidylinositol 3-kinase/Akt signaling pathway for the effect of nicotine on interleukin-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis

被引：61

作者：

Zheng, Xinpeng ^{[1
,2
]}

Xia, Chun ^{[1
]}

Chen, Zhongyi ^{[1
,3
]}

Huang, Jiagu ^{[1
,4
]}

Gao, Fengguang ^{[2
]}

Li, Guideng ^{[5
]}

Zhang, Bing ^{[2
]}

机构：

[1] Xiamen Univ, Zhongshan Hosp, Xiamen 361004, Fujian, Peoples R China

[2] Xiamen Univ, Sch Med, Xiamen 361005, Fujian, Peoples R China

[3] Second Hosp Xiamen, Xiamen, Fujian, Peoples R China

[4] Ningde Municipal Hosp, Ningde, Fujian, Peoples R China

[5] Univ Calif Irvine, Sch Med, Inst Immunol, Irvine, CA 92717 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 423卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Nicotine; IL-1 beta-stimulated chondrocytes; PI3K/Akt pathway; Cell apoptosis; MATRIX METALLOPROTEINASE-13 EXPRESSION; ARTICULAR CHONDROCYTES; CARTILAGE; DEATH; CELLS; ACTIVATION; GROWTH; PHOSPHORYLATION; INHIBITOR; SURVIVAL;

D O I：

10.1016/j.bbrc.2012.06.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Chondrocyte apoptosis is mainly responsible for the progressive degeneration of cartilage in osteoarthritis (OA). Interleukin-1beta (IL-1 beta) was widely used as a modulating and chondrocyte apoptosis-inducing agent. Nicotine is able to confer resistance to apoptosis and promote cell survival in some cell lines, but its regulatory mechanism is ambiguous. We aimed to investigate the effect of nicotine on IL-1 beta-induced chondrocyte apoptosis and the mechanism underlying how nicotine antagonizes IL-1 beta-induced apoptosis of rat chondrocytes. Chondrocytes isolated from newborn rat joints were exposed to IL-1 beta. The cell viability was analyzed by the MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide) assay, and the apoptotic cells were counted with DAPI staining. The levels of Akt, phosphorylated-Akt (p-Akt) and downstream protein targets of Akt were detected by western blotting. The results showed that nicotine neutralized the effect of IL-1 beta on chondrocytes by activating PI3K/Akt signaling pathways, including the PI3K/Akt/Bcl-2 pathway, to block IL-1 beta-induced cell apoptosis and the PI3K/Akt/p70S6K (p70S6 kinase)/S6 pathway for promoting protein synthesis, modulating its downstream effectors such as TIMP-1 and MMP-13. Activation of the PI3K/Akt pathway is, in part, required for the effect of nicotine on IL-1 beta-induced chondrocyte apoptosis in a rat model of osteoarthritis. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：606 / 612

页数：7

共 43 条

[21]

Embedded together: The life and death consequences of interaction of the Bcl-2 family with membranes [J].