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) |