Suppression of interleukin-1 beta-converting enzyme-mediated cell death by insulin-like growth factor

Abstract

COS cells are resistant to cell death induced either by interleukin-1beta-converting enzyme (*ICE) and ICE homolog (ICH-1L) overexpression or by serum deprivation. COS cells deprived of serum undergo apoptosis after transfection with an ICE expression construct, but not an ICH-1L construct. ICE-mediated apoptosis of COS cells in serum-free medium is suppressed by insulin-like growth factor (IGF)-1 and insulin. Viability of Rat-1 cell line (Rat-1/ICE) expressing low levels of ICE-LacZ fusion protein is lower than those of cell lines expressing either both Bcl-2 and ICE or mutant ICEGly-->Ser during serum deprivation. Enzymatic activation and processing of ICE are observed in cells induced to die by serum deprivation, which are suppressed by IGF-1. IGF-1 or insulin suppresses ICE-mediated cell death without affecting the expression levels of Bcl-2, Bcl-x, or Bax. 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 independent of the expression of Bcl-2, Bcl-x, or Bax.