The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

Molecules

Beiru Zhang³  Xiaohui Bian³  Ping He³  Xiaoying Fu²  Keiichi Higuchi¹  Xu Yang³ 

[1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Shinshu University, 3-1-1, Asahi, Matsumoto 390-8621, Japan; E-Mail:;Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; E-Mail:;Department of Nephrology, Shengjing Hospital, China Medical University, Shenyang 110004, China; E-Mails:

关键词: Alzheimer’s disease (AD);    β-amyloid (Aβ);    rat cardiac myocyte;    ER-stess;    p38;   

DOI  :  10.3390/molecules190812242

来源: mdpi

【 摘 要 】

β-Amyloid (Aβ) is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer’s disease (AD). Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ_25–35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ_25–35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ_25–35 played a critical role in cardiac myocytes, suggesting that Alzheimer’s disease (AD) had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.