bFGF rescues 423-cells from serum starvation-induced apoptosis downstream of activated caspase-3.
Serum withdrawal rapidly induces apoptosis in rat 423-cells, while addition of bFGF results in cell survival. However, surviving cells initially display morphological changes characteristic for apoptotic cells and even process caspases. Active caspase-3 was detected at the single-cell level in those finally bFGF-rescued cells, while mitochondrial integrity was maintained. Generation of cleavage products of caspase targets was confirmed in surviving cells. Proteome analysis indicated multi-faceted survival activities of bFGF including upregulation of inhibitor-of-apoptosis and heat shock protein family members directly interfering with caspases. Our data suggest that the "point-of-no-return" in death-induced cells has to be moved downstream of activated caspase-3.
Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria. chantal.schamberger@meduniwien.ac.at
Chantal J
CJ
Schamberger
Christopher
C
Gerner
Christa
C
Cerni
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D051381:Rats
D016895:Culture Media, Serum-Free; D006360:Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D020543:Proteome; D016222:Fibroblast Growth Factor 2; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases