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学科主题基础医学
Cardioprotection by CaMKII-delta B Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70
Peng, Wei2; Zhang, Yan2,3; Zheng, Ming2; Cheng, Heping2; Zhu, Weizhong; Cao, Chun-Mei2; Xiao, Rui-Ping1
关键词CaMKII isoforms CaMKII-delta B oxidative stress hypoxia cardiomyocyte apoptosis iHSP70 HSF1
刊名CIRCULATION RESEARCH
2010-01-08
DOI10.1161/CIRCRESAHA.109.210914
106期:1页:102-110
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
资助者Peking University ; 973 Program ; NIH ; National Institute on Aging ; Peking University ; 973 Program ; NIH ; National Institute on Aging
研究领域[WOS]Cardiovascular System & Cardiology ; Hematology
关键词[WOS]CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE ; MUSCLE CELL APOPTOSIS ; TRANSCRIPTION FACTOR ; CARDIAC-HYPERTROPHY ; IN-VIVO ; BETA(1)-ADRENERGIC STIMULATION ; DILATED CARDIOMYOPATHY ; INDEPENDENT ACTIVATION ; VENTRICULAR MYOCYTES ; INHIBITION PROTECTS
英文摘要

Rationale: Ca(2+)/calmodulin-dependent protein kinase (CaMK)II is a multifunctional kinase involved in vital cellular processes such as Ca(2+) handling and cell fate regulation. In mammalian heart, 2 primary CaMKII isoforms, delta B and delta C, localize in nuclear and cytosolic compartments, respectively. Although previous studies have established an essential role of CaMKII-delta C in cardiomyocyte apoptosis, the functional role of the more abundant isoform, CaMKII-delta B, remains elusive.

Objective: Here, we determined the potential role of CaMKII-delta B in regulating cardiomyocyte viability and explored the underlying mechanism.

Methods and Results: In cultured neonatal rat cardiomyocytes, the expression of CaMKII-delta B and CaMKII-delta C was inversely regulated in response to H(2)O(2)-induced oxidative stress with a profound reduction of the former and an increase of the later. Similarly, in vivo ischemia/reperfusion (IR) led to an opposite regulation of these CaMKII isoforms in a rat myocardial IR model. Notably, overexpression of CaMKII-delta B protected cardiomyocytes against oxidative stress-, hypoxia-, and angiotensin II-induced apoptosis, whereas overexpression of its cytosolic counterpart promoted apoptosis. Using cDNA microarray, real-time PCR and Western blotting, we demonstrated that overexpression of CaMKII-delta B but not CaMKII-delta C elevated expression of heat shock protein (HSP)70 family members, including inducible (i)HSP70 and its homolog (Hst70). Moreover, overexpression of CaMKII-delta B led to phosphorylation and activation of heat shock factor (HSF)1, the primary transcription factor responsible for HSP70 gene regulation. Importantly, gene silencing of iHSP70, but not Hst70, abolished CaMKII-delta B-mediated protective effect, indicating that only iHSP70 was required for CaMKII-delta B elicited antiapoptotic signaling.

Conclusions: We conclude that cardiac CaMKII-delta B and CaMKII-delta C were inversely regulated in response to oxidative stress and IR injury, and that in contrast to CaMKII-delta C, CaMKII-delta B serves as a potent suppressor of cardiomyocyte apoptosis triggered by multiple death-inducing stimuli via phosphorylation of HSF1 and subsequent induction of iHSP70, marking both CaMKII-delta isoforms as promising therapeutic targets for the treatment of ischemic heart disease. (Circ Res. 2010;106:102-110.)

语种英语
所属项目编号2007CB512100
资助者Peking University ; 973 Program ; NIH ; National Institute on Aging ; Peking University ; 973 Program ; NIH ; National Institute on Aging
WOS记录号WOS:000273403600018
引用统计
被引频次:61[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67215
专题北京大学基础医学院_心血管所
作者单位1.NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA
2.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
3.Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
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GB/T 7714
Peng, Wei,Zhang, Yan,Zheng, Ming,et al. Cardioprotection by CaMKII-delta B Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70[J]. CIRCULATION RESEARCH,2010,106(1):102-110.
APA Peng, Wei.,Zhang, Yan.,Zheng, Ming.,Cheng, Heping.,Zhu, Weizhong.,...&Xiao, Rui-Ping.(2010).Cardioprotection by CaMKII-delta B Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70.CIRCULATION RESEARCH,106(1),102-110.
MLA Peng, Wei,et al."Cardioprotection by CaMKII-delta B Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70".CIRCULATION RESEARCH 106.1(2010):102-110.
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