Abstract
We have studied the expression of XIAP, cIAP-1 and cIAP-2 in fetal rat hepatocytes and its possible regulation by pro-apoptotic stimuli (transforming growth factor-beta (TGF-beta)) and survival signals (epidermal growth factor (EGF)). The three forms of inhibitor of apoptosis proteins (IAPs) are expressed in fetal hepatocytes and only cIAP-1, but not XIAP or cIAP-2, is cleaved during TGF-beta-induced apoptosis. The pan-caspase inhibitor Z-VAD.fmk blocked this effect, which indicates that cIAP-1 is a caspase substrate. EGF plays a dual role in the regulation of IAPs expression. On one hand, it increases cIAP-1 and cIAP-2 basal expression and, on the other hand, it blocks the cleavage of cIAP-1 by caspases induced by TGF-beta.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Chloromethyl Ketones / pharmacology
-
Animals
-
Apoptosis / drug effects*
-
Apoptosis / physiology
-
Caspase 3
-
Caspase Inhibitors
-
Caspases / metabolism*
-
Cells, Cultured
-
Cysteine Proteinase Inhibitors / metabolism*
-
DNA / drug effects
-
DNA / metabolism
-
Dose-Response Relationship, Drug
-
Fetus
-
Hepatocytes / cytology
-
Hepatocytes / drug effects*
-
Hepatocytes / metabolism
-
Proteins / metabolism*
-
Rats
-
Rats, Wistar
-
Time Factors
-
Transforming Growth Factor beta / pharmacology*
-
X-Linked Inhibitor of Apoptosis Protein
Substances
-
Amino Acid Chloromethyl Ketones
-
Caspase Inhibitors
-
Cysteine Proteinase Inhibitors
-
Proteins
-
Transforming Growth Factor beta
-
X-Linked Inhibitor of Apoptosis Protein
-
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
-
DNA
-
Casp3 protein, rat
-
Caspase 3
-
Caspases