Caspase-3 is activated and rapidly released from human umbilical vein endothelial cells in response to lipopolysaccharide
| Autor: | Ken-ichi Tanamoto, Toshikazu Shioiri, Masashi Muroi, Masato Nishida, Michio Kaminishi, Yoshikazu Mimura, Toshihisa Ogawa, Fumihiko Hatao, Yasuyuki Seto |
|---|---|
| Přispěvatelé: | Musashino University, Musashino University [Tokyo], Department of Metabolic Care and Gastrointestinal Surgery, The University of Tokyo (UTokyo), Showa General Hospital |
| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Umbilical Veins Time Factors Lipopolysaccharide HE-SFM Intracellular Space MTS Apoptosis FBS Umbilical vein CHX chemistry.chemical_compound Mice 0302 clinical medicine HUVEC Endotoxin LBP PBS Cells Cultured Caspase 7 0303 health sciences Caspase 3 sCD14 Endothelial stem cell Biochemistry Molecular Medicine Infection Intracellular Subcellular Fractions Programmed cell death LPS LDH Cell Survival Cycloheximide Biology 03 medical and health sciences Toll-like receptor TLR Sepsis Animals Humans Molecular Biology 030304 developmental biology sMD-2 L-Lactate Dehydrogenase Endothelial Cells Molecular biology Enzyme Activation chemistry 030215 immunology |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2009, 1792 (10), pp.1011. ⟨10.1016/j.bbadis.2009.06.006⟩ |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2009.06.006 |
| Popis: | International audience; Endothelial cell injury/dysfunction is considered to play a critical role in the pathogenesis of sever 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 hr 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. |
| Databáze: | OpenAIRE |
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