SUPPRESSION OF INTERLEUKIN-1-BETA-CONVERTING ENZYME-MEDIATED CELL-DEATH BY INSULIN-LIKE GROWTH-FACTOR

COS cells are resistant to cell death induced either by interleukin-1 beta-converting enzyme (ICE) and ICE homolog (ICH-1(L)) overexpressio n or by serum deprivation. Cos cells deprived of serum undergo apoptos is after transfection with an ICE expression construct, but not an ICE -1(L) construct. ICE-mediated apoptosis of COS cells in serum-free med ium is suppressed by insulin-like growth factor (IGF)-1 and insulin. V iability of Rat-1 cell line (Rat-1/ICE) expressing low levels of ICE-L acZ fusion protein is lower than those of cell lines expressing either both Bcl-2 and ICE or mutant ICE(Gly-->Ser) during serum deprivation, Enzymatic activation and processing of ICE are observed in cells indu ced to die by serum deprivation, which are suppressed by IGF-1. IGF-1 or insulin suppresses IGE-mediated cell death without affecting the ex pression levels of Bcl-2, Bcl-x, or Bar. Taken together, these results indicate that ICE is activated by growth factor deprivation, and IGF- 1 is able to suppress ICE-mediated cell death through a mechanism inde pendent of the expression of Bcl-2, Bcl-x, or Bar.