RRC ID 19620
著者 Shioiri T, Muroi M, Hatao F, Nishida M, Ogawa T, Mimura Y, Seto Y, Kaminishi M, Tanamoto K.
タイトル Caspase-3 is activated and rapidly released from human umbilical vein endothelial cells in response to lipopolysaccharide.
ジャーナル Biochim Biophys Acta
Abstract 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 LPS 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 LPS. This increase in caspase-3/7 activity was observed even when LDH release was undetected. These results indicate that caspase-3 is activated by LPS 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.
巻・号 1792(10)
ページ 1011-8
公開日 2009-10-1
DOI 10.1016/j.bbadis.2009.06.006
PII S0925-4439(09)00137-9
PMID 19559790
MeSH Animals Caspase 3 / metabolism* Caspase 7 / metabolism Cell Survival / drug effects Cells, Cultured Endothelial Cells / cytology Endothelial Cells / drug effects* Endothelial Cells / enzymology Endothelial Cells / metabolism* Enzyme Activation / drug effects Humans Intracellular Space / drug effects Intracellular Space / enzymology L-Lactate Dehydrogenase / metabolism Lipopolysaccharides / pharmacology* Mice Subcellular Fractions / drug effects Subcellular Fractions / enzymology Time Factors Umbilical Veins / cytology*
IF 3.411
引用数 17
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)