Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway
Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway
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高级氧化蛋白产物通过高级糖基化终产物介导的、氧化还原依赖性内在凋亡途径的受体诱导软骨细胞凋亡
DOI：
10.1007/s10495-015-1191-4
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发表时间：
2015-10
期刊：
影响因子：
7.2
通讯作者：
Chen JT
中科院分区：
文献类型：
--
作者：
Wu Qian;Zhong Zhao-Ming;Zhu Si-Yuan;Liao Cong-Rui;Zheng Shuai;Ding Ruo-Ting;Ye Qing;Ye Wen-Bin;Li Wei;Chen Jian-Ting;Pan Ying;Zeng Ji-Huan;Lin Qing-Song;Chen JT
类风湿关节炎（RA）的发生发展过程中，促炎性激素诱导的软骨细胞凋亡是软骨破坏的主要原因。晚期氧化蛋白产物（AOPPs）是一种新型的促炎介质，已被证实在RA患者体内蓄积。然而，AOPPs积累对软骨细胞凋亡的影响及其相关的细胞机制尚不清楚。目前的研究表明，AOPPs在RA大鼠血浆中的形成比正常增加。体外培养软骨细胞，用AOPPs修饰的大鼠血清白蛋白（AOPPs-RSA）处理。AOPPs可激活软骨细胞中的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶，并增加NADPH氧化酶亚基的表达，这是由晚期糖基化终末产物（AGEs）受体介导的，而不是清道夫受体CD 36。此外，AOPPs刺激可引起NADPH氧化酶依赖的ROS产生，从而导致线粒体功能障碍和内质网应激，进而激活caspase家族，最终导致细胞凋亡。最后，阻断CD 36而不是CD 36，大大减弱了这些信号。本研究首次证实AOPPs通过RAGE介导的氧化还原依赖的内源性凋亡途径诱导软骨细胞凋亡。这些数据表明AOPP可能是导致RA进展的一种新的致病因素。靶向AOPP触发的细胞机制可能成为RA患者有希望的治疗选择。
Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
5.5
作者：
Stamp, Lisa K.;Khalilova, Irada;Kettle, Anthony J.
通讯作者：
Kettle, Anthony J.
影响因子：
4.3
作者：
Kendra N. Reed;G. Wilson;A. Pearsall;V. Grishko
通讯作者：
Kendra N. Reed;G. Wilson;A. Pearsall;V. Grishko
影响因子：
19.6
作者：
WitkoSarsat, V;Friedlander, M;DescampsLatscha, B
通讯作者：
DescampsLatscha, B
影响因子：
3.6
作者：
Zhong ZM;Li T;Xu ZX;Meng TT;Zeng JH;Zheng S;Ye WB;Wu Q;Chen JT
通讯作者：
Chen JT