Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury.
Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury.
复制标题
热休克蛋白72通过增加肾缺血/再灌注损伤中X连锁凋亡抑制蛋白的稳定性来抑制细胞凋亡
DOI：
10.3892/mmr.2014.2939
复制
发表时间：
2015-03
影响因子：
3.4
通讯作者：
Mao H
中科院分区：
文献类型：
--
作者：
Zhang B;Rong R;Li H;Peng X;Xiong L;Wang Y;Yu X;Mao H
X连锁凋亡抑制蛋白（XIAP）在线粒体后水平负调控凋亡途径。XIAP通过直接结合和抑制特异性半胱天冬酶的活化而发挥作用。在细胞凋亡刺激后，线粒体第二线粒体源性半胱天冬酶激活剂（Smac）/具有低PI的直接IAP结合蛋白（DIABLO）被释放到胞质溶胶中，这导致XIAP从半胱天冬酶的置换。热休克蛋白72（Heat shock protein 72，HSP 72）是一种抗凋亡蛋白，可预防急性肾缺血/再灌注（I/R）引起的线粒体损伤，其在Smac/DIABLO和XIAP信号通路中的作用尚不清楚。在本研究中，HSP 72在体内和体外防止XIAP降解的假设进行了评估。为此，本研究采用大鼠I/R损伤模型，观察了HSP 72特异性诱导剂香叶基香叶基丙酮（GGA）对HSP 72肾保护作用的影响。HSP 72的细胞保护特性的机制也进行了研究，在体外使用腺病毒介导的过表达HSP 72在三磷酸腺苷（ATP）耗尽的人肾2（HK-2）细胞。GGA预处理大鼠可减轻I/R损伤后的肾小管细胞损伤、减少细胞凋亡、保留XIAP蛋白含量并改善肾功能。进行了体外研究，其中将细胞瞬时暴露于无葡萄糖培养基中的5 mM氰化钠以诱导细胞凋亡。与对照组相比，HSP 72过表达抑制了线粒体Smac/DIABLO的释放，并增加了ATP耗竭的HK-2细胞中XIAP和pro-caspase 3的水平。此外，HSP 72与Smac/DIABLO相互作用。目前的数据表明，HSP 72通过其抗细胞凋亡作用在I/R损伤中保护肾功能，所述抗细胞凋亡作用通过抑制线粒体Smac/DIABLO释放和保护XIAP蛋白含量起作用。
X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic pathways at a post-mitochondrial level. XIAP functions by directly binding and inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low PI (DIABLO) is released into the cytosol, which results in displacement of XIAP from caspases. Heat shock protein 72 (HSP72), an anti-apoptotic protein, prevents mitochondrial injury resulting from acute renal ischemia/reperfusion (I/R), its role in Smac/DIABLO and XIAP signaling remains to be elucidated. In the present study, the hypothesis that HSP72 prevents XIAP degradation in vivo and in vitro was assessed. To this purpose, a rat model of I/R injury was used to investigate the renoprotective role of HSP72 by treatment with geranylgeranylacetone (GGA), a specific inducer of HSP72. The mechanism of the cytoprotective properties of HSP72 was also investigated in vitro using adenovirus-mediated overexpression of HSP72 in adenosine triphosphate (ATP)-depleted human kidney 2 (HK-2) cells. Pre-conditioning rats with GGA attenuated renal tubular cell damage, reduced cell apoptosis, preserved XIAP protein content and improved renal function following I/R injury. An in vitro study was performed in which cells were transiently exposed to 5 mM sodium cyanide in a glucose-free medium in order to induce apoptosis. Compared with the control, overexpression of HSP72 inhibited Smac/DIABLO release from the mitochondria and increased levels of XIAP and pro-caspase 3 in ATP-depleted HK-2 cells. In addition, HSP72 interacted with Smac/DIABLO. The present data demonstrates that HSP72 preserves renal function in I/R injury through its anti-apoptotic effects, which act by suppressing mitochondrial Smac/DIABLO release and preserving XIAP protein content.
登录
查看更多内容
影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
影响因子：
4.8
作者：
Song, ZY;Yao, XB;Wu, M
通讯作者：
Wu, M
影响因子：
8.3
作者：
Tan Z;Turner RC;Leon RL;Li X;Hongpaisan J;Zheng W;Logsdon AF;Naser ZJ;Alkon DL;Rosen CL;Huber JD
通讯作者：
Huber JD
影响因子：
19.6
作者：
Kaushal, GP;Basnakian, AG;Shah, SV
通讯作者：
Shah, SV
影响因子：
56.9
作者：
Yang, Y;Fang, SY;Ashwell, JD
通讯作者：
Ashwell, JD