Regulation of heat shock protein 60 and 72 expression in the failing heart.
Regulation of heat shock protein 60 and 72 expression in the failing heart.
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DOI：
10.1016/j.yjmcc.2009.11.009
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发表时间：
2010-02
影响因子：
5
通讯作者：
Knowlton AA
中科院分区：
文献类型：
--
作者：
Wang Y;Chen L;Hagiwara N;Knowlton AA
心力衰竭是一种进行性的、致命的心肌疾病，是一种慢性炎症和损伤的状态。热休克蛋白（HSP）72是一种普遍存在的保护性蛋白质，具有良好的心脏保护作用，在心力衰竭中不会增加。相比之下，HSP 60水平在衰竭的心脏中增加了一倍。我们假设HSF-1在心力衰竭中没有被激活，而HSP 60的表达增加是由NFκB激活驱动的。为了验证这一假设，我们测量了热休克因子（HSF）-1和-2的水平，这是控制HSP表达的转录因子，在心力衰竭中增加。HSF-1中丝氨酸230或丝氨酸303/307的磷酸化没有增加，这被认为是调节其活性的; EMSA显示心力衰竭时HSF结合活性没有增加。尽管如此，HSP 60的mRNA增加，而不是HSP 72。与HSF相比，NFκB活性在心力衰竭时升高。HSP 60含有NFκB结合元件，而HSP 72不含。ChIP法显示NFκB与心力衰竭HSP 60基因中的两个NFκB结合元件的结合增加。用TNFα处理检测NFκB活化在心肌细胞系中HSP 60表达中的作用。TNFα可增加HSP 60的表达，而抑制p65表达的siRNA可抑制TNF α的作用。总之，心力衰竭时HSP 72没有增加，因为HSF活性没有改变; HSP 60的表达增加可能是由NFκB激活驱动的。
Heart failure, a progressive, fatal disease of the heart muscle, is a state of chronic inflammation and injury. Heat shock protein (HSP) 72, a ubiquitous protective protein that is well-established as cardioprotective, is not increased in heart failure. In contrast, HSP60 levels are doubled in the failing heart. We hypothesized that HSF-1 is not activated in heart failure and that the increased expression of HSP60 was driven by NFκB activation. To test this hypothesis, we measured levels of heat shock factor (HSF) −1 and −2, the transcription factors controlling HSP expression, which were increased in heart failure. There was no increased phosphorylation of serine 230 or serine 303/307 in HSF-1, which are thought to regulate its activity; EMSA showed no increase in HSF binding activity with heart failure. Nonetheless, mRNA was increased for HSP60, but not HSP72. In contrast to HSF, NFκB activity was increased in heart failure. HSP60, but not HSP72, contained NFκB binding elements. ChIP assay demonstrated increased binding of NFκB to both of the NFκB binding elements in the heart failure HSP60 gene. TNFα treatment was used to test the role of NFκB activation in HSP60 expression in a cardiac cell line. TNFα increased HSP60 expression, and this could be prevented by pretreatment with siRNA inhibiting p65 expression. In conclusion, HSP72 is not increased in heart failure because HSF activity is not changed; increased expression of HSP60 may be driven by NFκB activation.
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影响因子：
5.3
作者：
Kline, MP;Morimoto, RI
通讯作者：
Morimoto, RI
DOI：
10.1152/ajpheart.01175.2005
发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.82.19.6455
发表时间：
1985-01-01
影响因子：
11.1
作者：
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通讯作者：
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