EXPRESSION OF INDUCIBLE STRESS PROTEIN-70 IN RAT-HEART MYOGENIC CELLS CONFERS PROTECTION AGAINST SIMULATED ISCHEMIA-INDUCED INJURY
EXPRESSION OF INDUCIBLE STRESS PROTEIN-70 IN RAT-HEART MYOGENIC CELLS CONFERS PROTECTION AGAINST SIMULATED ISCHEMIA-INDUCED INJURY
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DOI：
10.1172/jci117030
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发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
DILLMANN, WH
中科院分区：
文献类型：
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作者：
MESTRIL, R;CHI, SH;DILLMANN, WH
心肌缺血显著增加应激/热休克蛋白（HSP）家族的几个成员的表达，特别是诱导型HSP 70亚型。热休克蛋白70的表达增加已被证明对致死性热休克发挥保护作用。我们已经使用大鼠胚胎心脏来源的细胞系H9 c2（2-1）在体外研究了利用这种对致死性热休克的抗性作为对缺血样应激的保护作用的可能性。发现其中热休克蛋白已被先前的热休克诱导的肌原性细胞变得对随后的模拟缺血应激具有抗性。此外，为了解决HSP 70的存在对这种保护作用有多大贡献的问题，我们已经产生了过表达人诱导型HSP 70的稳定转染的细胞系。胚胎大鼠心脏衍生的H9 c2（2-1）细胞用于此目的。发现该稳定转染的细胞系比仅表达选择标记（新霉素）的对照肌原细胞或亲本细胞系H9 c2（2-1）显著更耐缺血样应激。这一发现暗示了诱导型HSP 70蛋白在保护心肌细胞免受缺血性损伤中起主要作用。
Myocardial ischemia markedly increases the expression of several members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms. Increased expression of HSP70 has been shown to exert a protective effect against a lethal heat shock. We have examined the possibility of using this resistance to a lethal heat shock as a protective effect against an ischemic-like stress in vitro using a rat embryonic heart-derived cell line H9c2(2-1). Myogenic cells in which the heat shock proteins have been induced by a previous heat shock are found to become resistant to a subsequent simulated ischemic stress. In addition, to address the question of how much does the presence of the HSP70 contribute to this protective effect, we have generated stably transfected cell lines overexpressing the human-inducible HSP70. Embryonal rat heart-derived H9c2(2-1) cells were used for this purpose. This stably transfected cell line was found to be significantly more resistant to an ischemic-like stress than control myogenic cells only expressing the selectable marker (neomycin) or the parental cell line H9c2(2-1). This finding implicates the inducible HSP70 protein as playing a major role in protecting cardiac cells against ischemic injury.