Involvement of interleukin‐1β‐converting enzyme in apoptosis of bFGF‐deprived murine aortic endothelial cells

Abstract

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.

Inhibition of caspase proteases by CrmA enhances the resistance of human leukemic cells to multiple chemotherapeutic agents

“…34 Subsequent investigations have can initiate events leading to its own death via apoptosis. [1][2][3][4][5] shown that the caspase inhibitor acetyl-YVAD-chloromethyl Apoptosis is an active form of cell suicide that is characterized ketone (Ac-YVAD-CMK) inhibits the kinetics of cell death and by cell shrinkage, membrane blebbing, chromatin conden-DNA fragmentation in CP-treated malignant glioma cells 35 or sation, and DNA fragmentation. [6][7][8] Although these hallmark VP-16-treated HL-60 cells, 36 and benzyloxycarbonyl-VADfeatures are commonly observed in drug-induced apoptosis, fluoromethyl ketone (Z-VAD-FMK) inhibits the rate of cell relatively little is known about the signaling pathways which death in VP-16-treated THP.1 human monocytic cells.…”

“…For our experiments, cells were treated with 20 M VP-16 for 6 h, followed by preparation of cytosolic extracts. The extracts were then assayed for their ability to cleave in vitro translated 35 S-PARP into characteristic fragments of 85 and 24 kDa. As shown in Figure 2, extracts from Vector cells efficiently cleaved 35 S-PARP protein (lanes 2 and 4).…”

“…The extracts were then assayed for their ability to cleave in vitro translated 35 S-PARP into characteristic fragments of 85 and 24 kDa. As shown in Figure 2, extracts from Vector cells efficiently cleaved 35 S-PARP protein (lanes 2 and 4). This cleavage was drug-specific, since treatment of cells with DMSO, the drug diluent, had little effect (lanes 1 and 3).…”

“…For example, Ac-YVAD-CMK lar basis for the development of drug resistance is unknown. In cell culture, studies using tetrapeptide inhibitors have inhibits DNA fragmentation and the kinetics of apoptosis in CP-treated malignant glioma cells 35 or VP-16-treated HL-60 examined only the short-term consequences of inhibiting caspase proteases in drug-treated cells. By achieving constitutive cells, 36 and Z-VAD-FMK inhibits the rate of cell death in VP-16-treated THP.1 cells.…”

Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis

“…Human glioblastoma U87-MG (wild-type p53, Kondo et al, 1996) and U251-MG cells (mutant p53, Van Meir et al, 1994) were used in this study. Tumor cells were cultured in Dulbecco's modi®ed Eagle's medium (GIBCO BRL, Grand Island, NY) supplemented with 10% heat-inactivated fetal calf serum (GIBCO BRL), 4 mM glutamine, 50 U/ml penicillin and 50 mg/ml streptomycin.…”