Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.
Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.
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DOI：
10.1161/circresaha.109.209643
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发表时间：
2009-12-04
影响因子：
20.1
通讯作者：
Knowlton AA
中科院分区：
文献类型：
--
作者：
Kim SC;Stice JP;Chen L;Jung JS;Gupta S;Wang Y;Baumgarten G;Trial J;Knowlton AA
以前，我们已经发现细胞内HSP60位置的变化与细胞凋亡有关。HSP60已被报道为Toll样受体(TLR)4的配基，我们推测细胞外HSP60(ExHSP60)可能通过TLR-4介导细胞凋亡。用重组人HSP60或从损伤大鼠心肌细胞培养液中纯化的HSP60处理成年大鼠心肌细胞。ExHSP60诱导心肌细胞凋亡，表现为caspase3活性升高和DNA片段化增加。阻断TLR4抗体和核因子κB结合诱骗能减少细胞凋亡，但不能完全抑制，即使类似的处理阻断了内毒素诱导的细胞凋亡。三个不同的对照显示，除了exHSP60之外，没有证据表明有一种配体参与了细胞凋亡的调节。这是HSP60通过Toll样受体诱导细胞凋亡的首次报道。HSP60介导的TLR-4的激活可能是心力衰竭时心肌细胞丢失的机制之一，在血浆中已检测到HSP60。
Previously, we have found that changes in the location of intracellular HSP60 are associated with apoptosis. HSP60 has been reported to be a ligand of Toll-like receptor (TLR)4. We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR-4. Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP60 induced apoptosis in cardiac myocytes, as detected by increased caspase 3 activity and increased DNA fragmentation. Apoptosis could be reduced by blocking antibodies to TLR-4 and by NFκB binding decoys, but not completely inhibited, even though similar treatment blocked LPS-induced apoptosis. Three distinct controls showed no evidence for involvement of a ligand other than exHSP60 in the mediation of apoptosis. This is the first report of HSP60-induced apoptosis via the toll-like receptors. HSP60 mediated activation of TLR-4 may be a mechanism of myocyte loss in heart failure, where HSP60 has been detected in the plasma.