Apoptotic signaling in endothelial cells with neutrophil activation.
Apoptotic signaling in endothelial cells with neutrophil activation.
复制标题
内皮细胞中的凋亡信号传导与中性粒细胞激活。
DOI：
10.1007/s11010-011-1179-5
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Suzuki K.
中科院分区：
文献类型：
--
作者：
Koshio O;Nagao T;Mabuchi A;Ono Y;Suzuki K.
与肿瘤坏死因子-α (TNF-α) 和白细胞介素-1β (IL-1β) 的情况一样，多形核白细胞 (PMN) 释放的脱颗粒物质 (DS) 和 H2O2 通过丝裂原激活蛋白激酶 (MAPK) 家族成员的磷酸化导致内皮细胞凋亡。研究发现，用 IL-1β 或 TNF-α/放线菌酮 (CHX) 刺激人脐静脉内皮细胞 (HUVEC) 可以以时间依赖性方式增强 p38 和 Jun-N 末端激酶 (JNK) 的磷酸化，但不影响细胞外信号调节激酶的时间依赖性磷酸化。此外，IL-1β 和 TNF-α/CHX 诱导激活转录因子 2 (ATF-2) 的磷酸化，但 c-Jun 不诱导。此外，HUVEC 中的 p38 会被 PMN 释放的 DS 以及 H2O2 磷酸化，但不会被 PMN 的髓过氧化物酶 (MPO) 诱导的·O2− 磷酸化。另一方面，HUVEC 中的 caspase 8 被 DS 激活，但不被 H2O2 和/或·O2− 激活。此外，半胱天冬酶3和7通过DS处理被裂解并转变成活性形式。 DS 被浓缩，通过电泳分析，发现含有 MPO 的前体和亚基（90、60 和 14 kDa）以及另一种分子量约为 28 kDa 的肽。由于p38 MAPK抑制剂SB203580不能抑制HUVEC中ATF-2的磷酸化，因此表明JNK在一系列信号传导过程中比p38更重要。这些结果表明，不仅TNF-α/CHX和IL-1β，而且PMN释放的DS和细胞可渗透的活性氧H2O2都可能通过内皮细胞凋亡诱导血管损伤。
As is the case for tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), degranulated substances (DS) released from polymorphonuclear leukocytes (PMN) and H2O2cause endothelial cell apoptosis through the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family. Stimulation of human umbilical vein endothelial cells (HUVEC) with IL-1β or TNF-α/cycloheximide (CHX) was found to enhance the phosphorylation of p38 and Jun-N-terminal kinase (JNK) in a time-dependent fashion, but did not affect the time-dependent phosphorylation of extracellular signal-regulated kinase. In addition, IL-1β and TNF-α/CHX induced the phosphorylation of activating transcription factor-2 (ATF-2), but not c-Jun. Moreover, the p38 in HUVEC was phosphorylated by DS released from PMN and also by H2O2, but not by •O2−induced by myeloperoxidase (MPO) of PMN. On the other hand, caspase 8 in HUVEC was activated by DS, but not by H2O2and/or •O2−. In addition, caspases 3 and 7 were cleaved by the treatment of DS and turned into active forms. DS was concentrated, analyzed by electrophoresis, and revealed to contain precursor and subunits of MPO (90, 60, and 14 kDa) and another peptide with a molecular weight of about 28 kDa. Because SB203580 that was an inhibitor of p38 MAPK did not repress phosphorylation of ATF-2 in HUVEC, it was suggested that JNK was more important than p38 in a series of signaling courses. These results suggest the possibility that not only TNF-α/CHX and IL-1β but also DS released from PMN and the cell-permeable reactive oxygen species H2O2induce blood vessel injury through endothelial apoptosis.