Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system
机构:[1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,6 Tiantan Xili,Beijing 100050,Peoples R China临床科室心血管中心[2]Capital Med Univ, Dept Physiol & Pathophysiol, Beijing 100069, Peoples R China[3]Dalian Med Univ, Inst Cardiovasc Dis, Affiliated Hosp 1, Dalian 116011, Peoples R China[4]Capital Med Univ, Beijing Tian Tan Hosp, Dept Cardiol, Dept Geriatr, Beijing 100050, Peoples R China
Aim: Apoptosis participated in the pathological process of myocardial ischemia/reperfusion (I/R) injury. Previous studies have reported that endogenous substance sRAGE protect against I/R injury through inhibiting myocardial apoptosis. But the mechanisms are currently unknown. Prior work has demonstrated that ubiquitin proteasome system (UPS) dysfunction is closely related to apoptosis. We explored the potential role of UPS in the effect of sRAGE inhibition on I/R-induced myocardial apoptosis. Methods and results: Adult male C57BL mice treated with sRAGE (100 mu g/day, i.p.) or saline were performed to ligate left anterior descending coronary artery (LAD) as an in vivo model. As an in vitro model, primary murine cardiomyocytes pretreated with sRAGE or sRAGE-containing adenovirus were simulated I/R by "ischemia buffer". The TUNEL and caspase-3 activity were assessed. Also the activity and expression of proteasome were detected. sRAGE decreased the number of TUNEL-positive cardiomyocytes and caspase-3 activity, however, the inhibition of sRAGE on I/R-induced apoptosis was abolished by proteasome inhibitor Bortezimb (BTZ). sRAGE inhibited the decreased proteasome activity, also the reduction in protein and gene levels of beta 1i and beta 5i following I/R. Suppression of STAT3 blocked the inhibition of sRAGE on apoptosis induced by I/R. The chromatin immunoprecipitation (CHIP) results confirmed that sRAGE promoted activating STAT3 binding to beta 1i and beta 5i promoter. Conclusions: Our data suggest that the inhibition of sRAGE on I/R-induced apoptosis is associated with activation and expression of proteasome, including improved proteasome activity and elevated beta 1i and beta 5i expression mediated by STAT3 activation. We predict that sRAGE is a novel intervention to target UPS activation for preventing and treating myocardial apoptosis. (C) 2016 Elsevier Inc. All rights reserved.
基金:
National Natural Science Foundation of China [30801217, 81370313, 81570321]; Beijing Nova Program [20108050]; Beijing Health System High Level Health Technical Personnel Training Program [2013-3-046]
基金编号:2013-3-0463080121720108050 81570321 81370313
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外文
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出版当年[2015]版:
大类|2 区医学
小类|2 区生化与分子生物学2 区内分泌学与代谢
最新[2023]版:
大类|2 区生物学
小类|2 区生化与分子生物学2 区内分泌学与代谢
第一作者:
第一作者机构:[1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,6 Tiantan Xili,Beijing 100050,Peoples R China[*1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,6 Tiantan Xili,Beijing 100050,Peoples R China
通讯作者:
通讯机构:[1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,6 Tiantan Xili,Beijing 100050,Peoples R China[*1]Capital Med Univ,Beijing Tian Tan Hosp,Dept Cardiol,6 Tiantan Xili,Beijing 100050,Peoples R China
推荐引用方式(GB/T 7714):
Guo Cai-xia,Jiang Xue,Zeng Xiang-jun,et al.Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system[J].FREE RADICAL BIOLOGY AND MEDICINE.2016,94:17-26.doi:10.1016/j.freeradbiomed.2016.02.011.
APA:
Guo, Cai-xia,Jiang, Xue,Zeng, Xiang-jun,Wang, Hong-xia,Li, Hui-hua...&Chen, Bu-xing.(2016).Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system.FREE RADICAL BIOLOGY AND MEDICINE,94,
MLA:
Guo, Cai-xia,et al."Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system".FREE RADICAL BIOLOGY AND MEDICINE 94.(2016):17-26