Caspase-3 is activated and rapidly released from human umbilical vein endothelial cells in response to lipopolysaccharide
Caspase-3 is activated and rapidly released from human umbilical vein endothelial cells in response to lipopolysaccharide
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DOI：
10.1016/j.bbadis.2009.06.006
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发表时间：
2009-10-01
影响因子：
6.2
通讯作者：
Tanamoto, Ken-ichi
中科院分区：
文献类型：
--
作者：
Shioiri, Toshikazu;Muroi, Masashi;Tanamoto, Ken-ichi
内皮细胞损伤/功能障碍被认为在严重脓毒症和脓毒性休克的发病机制中起关键作用。尽管认为内皮细胞凋亡参与内皮损伤/功能障碍。生理参与仍然不明确，因为细胞凋亡的诱导需要内源性细胞凋亡抑制剂的抑制。在这里，我们表明，caspase-3激活，细胞凋亡的生物学指标，观察到响应脂多糖（LPS）刺激，即使在内源性细胞凋亡抑制剂的影响下，激活的caspase-3是迅速释放从人脐静脉内皮细胞（HUVEC）在放线菌酮（CHX）的存在下，即使在LPS结合蛋白（LBP）的存在下，在HUVEC中，在刺激后长达24小时也没有检测到响应于LIPS的细胞内半胱天冬酶-3/7活性的增加。可溶性CD 14和可溶性MD-2，而以可溶性CD 14/LBP依赖性方式观察到细胞活力的降低和细胞酶乳酸脱氢酶（LDH）释放的增加。另一方面，即使在不存在CHX的情况下，caspase-3/7活性的显著增加和切割的caspase-3/7活性的显著增加，在培养上清液中观察到响应于LIPS的LDH释放轻微增加的3片段。即使当未检测到LDH释放时，也观察到半胱天冬酶-3/7活性的增加。这些结果表明，caspase-3在生理条件下被LIPS激活，并表明HUVEC通过快速释放激活的caspase-3进入细胞外空间来逃避细胞死亡。这种逃逸机制的失效可能导致内皮损伤/功能障碍（C）2009 Elsevier B V.保留所有权利
Endothelial cell injury/dysfunction is considered to play a critical role in the pathogenesis of severe sepsis and septic shock. Although it is considered that endothelial cell apoptosis is involved in endothelial injury/dysfunction. physiological involvement remains ambiguous since the induction of apoptosis requires the inhibition of endogenous apoptosis inhibitors. Here we show that caspase-3 activation, a biological indicator of apoptosis, is observed in response to lipopolysaccharide (LPS) Stimulation even under the influence of endogenous apoptosis inhibitors, and that activated caspase-3 is rapidly released from human umbilical vein endothelial cells (HUVEC) In the presence of cycloheximide (CHX), an increase in intracellular caspase-3/7 activity in response to LIPS was not detected in HUVEC up to 24 h following Stimulation even in the presence of LPS-binding protein (LBP). soluble CD14 and soluble MD-2, whereas the decrease in cell viability and increase in release of the cellular enzyme lactate dehydrogenase (LDH) were observed in a soluble CD14/LBP-dependent manner On the other hand, even in the absence of CHX, a significant increase in caspase-3/7 activity and a cleaved caspase-3 fragment with a slight increase in LDH release was observed in culture supernatants in response to LIPS This increase in caspase-3/7 activity was observed even when LDH release was undetected. These results indicate that caspase-3 is activated by LIPS under physiological conditions and suggest that HUVEC escape from cell death by rapidly releasing activated caspase-3 into extracellular space. Failure of this escape mechanism may result in endothelial injury/dysfunction (C) 2009 Elsevier B V. All rights reserved