Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling.
Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling.
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热应激通过阻断钙蛋白酶/p38 MAPK 信号传导来防止脂多糖诱导的肺微血管内皮细胞凋亡。
DOI：
10.1007/s10495-016-1263-0
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发表时间：
2016-08
期刊：
影响因子：
7.2
通讯作者：
Su, Lei
中科院分区：
文献类型：
--
作者：
Liu, Zhi-feng;Zheng, Dong;Fan, Guo-chang;Peng, Tianqing;Su, Lei
肺微血管内皮细胞（PMEC）损伤包括凋亡在脓毒症急性肺损伤的发病机制中起重要作用。我们最近的研究表明，钙蛋白酶激活有助于脓毒症条件下PMEC的凋亡。本研究探讨了钙蛋白酶激活如何介导细胞凋亡以及热应激是否调节脂多糖（LPS）刺激的PMECs中钙蛋白酶的激活。在培养的小鼠原代PMEC中，与LPS（1 μ g/ml，24 h）孵育增加了活性caspase-3片段和DNA片段，表明细胞凋亡。LPS的这些作用通过用热应激（43 ° C持续2小时）预处理而消除。LPS还诱导钙蛋白酶活化和p38 MAPK磷酸化增加。抑制calpain和p38 MAPK可防止LPS诱导的细胞凋亡。此外，抑制钙蛋白酶阻断p38 MAPK磷酸化在LPS刺激的PMECs。值得注意的是，热应激降低calpain-1/2和calpain活性的蛋白水平，并阻断p38 MAPK磷酸化响应LPS。此外，钙蛋白酶-1或钙蛋白酶-2的强制上调足以诱导PMEC中p38 MAPK磷酸化和凋亡，这两者都被热应激抑制。总之，热应激可阻止LPS诱导的PMEC凋亡。热应激的这种作用与钙蛋白酶表达和活化的下调以及随后响应于LPS的p38 MAPK活化的阻断有关。因此，阻断calpain/p38 MAPK通路可能是热应激介导的LPS刺激的内皮细胞凋亡抑制的新机制。
Pulmonary microvascular endothelial cells (PMECs) injury including apoptosis plays an important role in the pathogenesis of acute lung injury during sepsis. Our recent study has demonstrated that calpain activation contributes to apoptosis in PMECs under septic conditions. This study investigated how calpain activation mediated apoptosis and whether heat stress regulated calpain activation in lipopolysaccharides (LPS)-stimulated PMECs. In cultured mouse primary PMECs, incubation with LPS (1 µg/ml, 24 h) increased active caspase-3 fragments and DNA fragmentation, indicative of apoptosis. These effects of LPS were abrogated by pre-treatment with heat stress (43 °C for 2 h). LPS also induced calpain activation and increased phosphorylation of p38 MAPK. Inhibition of calpain and p38 MAPK prevented apoptosis induced by LPS. Furthermore, inhibition of calpain blocked p38 MAPK phosphorylation in LPS-stimulated PMECs. Notably, heat stress decreased the protein levels of calpain-1/2 and calpain activities, and blocked p38 MAPK phosphorylation in response to LPS. Additionally, forced up-regulation of calpain-1 or calpain-2 sufficiently induced p38 MAPK phosphorylation and apoptosis in PMECs, both of which were inhibited by heat stress. In conclusion, heat stress prevents LPS-induced apoptosis in PMECs. This effect of heat stress is associated with down-regulation of calpain expression and activation, and subsequent blockage of p38 MAPK activation in response to LPS. Thus, blocking calpain/p38 MAPK pathway may be a novel mechanism underlying heat stress-mediated inhibition of apoptosis in LPS-stimulated endothelial cells.
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影响因子：
2.2
作者：
Chen, G;Kelly, C;Bouchier-Hayes, D
通讯作者：
Bouchier-Hayes, D
影响因子：
3.1
作者：
Brinton, Mark R.;Tagge, Chad A.;Stewart, Russell J.;Cheung, Alfred K.;Shiu, Yan-Ting E.;Christensen, Douglas A.
通讯作者：
Christensen, Douglas A.
影响因子：
3.1
作者：
Farley, K. S.;Wang, L. F.;Mehta, S.
通讯作者：
Mehta, S.
影响因子：
3.7
作者：
Moulin, Maryline;Arrigo, Andre Patrick
通讯作者：
Arrigo, Andre Patrick
影响因子：
5
作者：
Gill, RR;Gbur, CJ;Sholley, MM
通讯作者：
Sholley, MM