Division of Cardiology, Department of Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 30 Bond St., Toronto, ON, Canada.
Amino Acids. 2011 Oct;41(4):843-7. doi: 10.1007/s00726-010-0527-1. Epub 2010 Mar 4.
S100B, a calcium-binding protein of the EF-hand type exerts both intracellular and extracellular functions. S100B is induced in the myocardium of human subjects and an experimental rat model following myocardial infarction. Forced expression of S100B in neonatal rat myocyte cultures, and high level expression of S100B in transgenic mice hearts and aortic smooth muscle cells inhibit cardiac hypertrophy and the associated phenotype, arterial smooth muscle proliferation, respectively, but demonstrate increased apoptosis following α(1)-adrenergic stimulation or myocardial infarction. Knocking out S100B, augmented hypertrophy, decreased apoptosis and preserved cardiac function following myocardial infarction. S100B induces apoptosis by an extracellular mechanism by interacting with the receptor for advanced glycation end products and activating ERK1/2 and p53 signaling. The intracellular, and extracellular, roles of S100B are attractive therapeutic targets for the treatment of both cardiac and vascular disease.
S100B 是一种 EF 手型钙结合蛋白，具有细胞内和细胞外功能。在心肌梗死后的人类和实验性大鼠模型中，心肌中会诱导 S100B 的产生。在新生大鼠心肌细胞培养物中强制表达 S100B，以及在转基因小鼠心脏和主动脉平滑肌细胞中高水平表达 S100B，分别抑制心脏肥大和相关表型、动脉平滑肌增殖，但在α(1)-肾上腺素能刺激或心肌梗死后表现出增加的细胞凋亡。敲除 S100B 后，心肌梗死后心肌肥大增加、细胞凋亡减少且心脏功能得以保留。S100B 通过与晚期糖基化终产物受体相互作用并激活 ERK1/2 和 p53 信号通路，通过细胞外机制诱导细胞凋亡。S100B 的细胞内和细胞外作用是治疗心脏和血管疾病的有吸引力的治疗靶点。
