Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes

Author:

Martin Jody L.1,Mestril Ruben1,Hilal-Dandan Randa1,Brunton Laurence L.1,Dillmann Wolfgang H.1

Affiliation:

1. From the Department of Medicine, Divisions of Endocrinology and Metabolism (J.L.M., R.M., W.H.D.) and Cardiology (L.L.B.) and Department of Pharmacology (R.H.-D., L.L.B.), University of California, San Diego.

Abstract

Background Overexpression of the inducible hsp70 protects against ischemic cardiac damage. However, it is unclear whether the small heat shock proteins hsp27 and αB-crystallin protect against ischemic injury. Methods and Results Our aim was to examine whether the overexpression of hsp27 and αB-crystallin in neonatal and adult rat cardiomyocytes would protect against ischemic injury. Recombinant adenovirus expressing hsp27 or αB-crystallin under the control of the cytomegalovirus promoter was used to infect cardiac myocytes at high efficiency as assessed by immunostaining. Overexpression was confirmed by Western blot analysis. Cardiomyocytes were subjected to simulated ischemic stress, and survival was estimated through assessment of lactate dehydrogenase and creatine phosphokinase release. The hsp27 overexpression decreased lactate dehydrogenase release by 45±7.5% in adult cardiomyocytes but had no effect in the neonatal cells. In contrast, αB-crystallin overexpression was associated with a decrease in cytosolic enzyme release in both adult (29±6.6%) and neonatal (32±5.4%) cardiomyocytes. Decreased endogenous hsp25 with an antisense adenovirus produced a 29±9.9% increase in damage with simulated ischemia. Overexpression of the inducible hsp70 in adult cardiomyocytes was associated with a 34±4.6% decrease in lactate dehydrogenase release and is in line with our previous results in neonatal cardiomyocytes. Conclusions The increased expression of hsp27 and αB-crystallin through an adenovirus vector system protects against ischemic injury in adult cardiomyocytes. Likewise, the overexpression of αB-crystallin protects against ischemic damage in neonatal cardiomyocytes. Decreasing the high levels of endogenous hsp25 present in neonatal cardiomyocytes renders them more susceptible to damage caused by simulated ischemia.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3