Involvement of interleukin-1 beta-converting enzyme in apoptosis of bFGF-deprived murine aortic endothelial cells.
Apoptosis (programmed cell death) is an essential physiological process that is genetically regulated and contributes to the balance between cell growth, differentiation, and the maintenance of normal cells. Recent studies show that deprivation of growth factor induces apoptosis in endothelial cells. However, the molecular mechanisms regulating apoptosis remain unclear. In this study, we demonstrate that deprivation of basic fibroblast growth factor (bFGF) increased the expression of interleukin-1 beta-converting enzyme (ICE) protein, and subsequently induced apoptosis in murine aortic endothelial (MAE) cells. In contrast, the proteins of the tumor suppressor p53 and c-myc were undetected during apoptosis. This apoptosis was suppressed by the tetrapeptide ICE inhibitor, Ac-YVAD-CMK. Overexpression of murine ICE, in addition, induced apoptosis in MAE cells using gene transfer techniques. These results strongly suggest that ICE may mediate apoptosis in bFGF-deprived endothelial cells, and the suppression of ICE function could represent a novel approach for the protection of endothelial cells from damages.-Kondo, S., Kondo, Y., Yin, D., Barnett, G. H., Kaakaji, R., Peterson, J. W., Morimura, T., Kubo, H., Takeuchi, J., Barna, B. P. Involvement of interleukin-1 beta converting enzyme in apoptosis of bFGF-deprived murine aortic endothelial cells.
Kondo
S
S
Department of Neurosurgery, Cleveland Clinic Foundation, Ohio 44195, USA.
Kondo
Y
Y
Yin
D
D
Barnett
G H
GH
Kaakaji
R
R
Peterson
J W
JW
Morimura
T
T
Kubo
H
H
Takeuchi
J
J
Barna
B P
BP
D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1; D002460:Cell Line; D002470:Cell Survival; D003374:Coumarins / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000502:physiology*; D015870:Gene Expression; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; C096022:acetyl-tyrosyl-valyl-alanyl-aspartyl-7-amino-4-methylcoumarinamide; D016222:Fibroblast Growth Factor 2; D003546:Cysteine Endopeptidases; D020170:Caspase 1