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-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.
Jung
Y
Y
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown, Massachusetts 02129, USA.
Miura
M
M
Yuan
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D020170:Caspase 1; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D017931:DNA Primers; D006133:Growth Substances / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis
D000906:Antibodies; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D006133:Growth Substances; D007328:Insulin; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D007334:Insulin-Like Growth Factor I; D001616:beta-Galactosidase; D003546:Cysteine Endopeptidases; D020170:Caspase 1