The heat shock paradox and cardiac myocytes: role of heat shock factor.
The heat shock paradox and cardiac myocytes: role of heat shock factor.
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DOI：
10.1097/shk.0b013e3182094a0b
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Knowlton AA
中科院分区：
文献类型：
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作者：
Kobba S;Kim SC;Chen L;Kim E;Tran AL;Knuefermann P;Knowlton AA
热休克反应的诱导被认为是一种保护性反应，减少损伤并改善细胞存活。然而，当炎症先于热休克时，损伤会意外增加，称为热休克悖论，这被假设为多器官功能障碍的潜在机制。我们假设热休克悖论将发生在成年心肌细胞和热休克因子（HSF）1将有助于损伤。42°C下的热休克（HS）和TNF（10 ng/ml）分别用作HS和炎性损伤。TNF和HS联合应用（TNF/HS）可引起成年大鼠心肌细胞凋亡。TNF/HS导致热休克蛋白（HSP）60的增加，与未经处理的细胞相比，那些接受HS/TNF，或TNF单独。在任何一组中，血红素加氧酶1都没有增加。HSP 72在所有组中均升高，TNF/HS组最高。TNF/HS组NFκB活化最强。在所有组中，用DNA结合HSF 1诱饵进行预处理可以防止HSP的增加并减少凋亡。然而，在所有治疗组中观察到的iNOS的增加不受HSF 1结合诱饵的影响。我们的结论是热休克悖论发生在成年心肌细胞，热休克悖论的一部分，热休克蛋白60增加，热休克因子1激活有助于损伤。
The induction of the heat shock response is accepted to be a protective response, reducing injury and improving cell survival. However, when inflammation precedes heat shock there is an unexpected increase in injury, known as the heat shock paradox, which is hypothesized to be a mechanism underlying multi-organ dysfunction. We hypothesized that the heat shock paradox would occur in adult cardiac myocytes and that heat shock factor (HSF)1 would contribute to injury. Heat shock (HS) at 42°C and TNF (10 ng/ml) were used as the HS and the inflammatory insult, respectively. The combination of TNF followed by HS (TNF/HS) caused the greatest amount of apoptosis in adult rat cardiac myocytes. TNF/HS resulted in an increase in heat shock protein (HSP) 60, compared to untreated cells, those receiving HS/TNF, or TNF alone. There was no increase in heme oxygenase 1 in any of the groups. HSP72 increased in all the groups, with the greatest levels with TNF/HS. NFκB activation was greatest with TNF/HS. Pretreatment with a DNA binding decoy for HSF1 prevented the increase in HSPs and decreased apoptosis in all groups. However, the increase in iNOS, seen in all treatment groups, was unaffected by the HSF1 binding decoy. We conclude that the heat shock paradox occurs in adult cardiac myocytes, that HSP60 is increased as part of the heat shock paradox, and that HSF1 activation contributes to injury.