Bcl-2 protects lymphoma cells from apoptosis but not growth arrest promoted by cAMP and dexamethasone.
Glucocorticoids or increases in cellular cAMP promote apoptosis in many cell types, including murine S49 cells. We examined the impact of Bcl-2, an antiapoptotic protein, on S49 cell growth and death promoted by the glucocorticoid dexamethasone or agents that increase cAMP: isoproterenol (a beta-adrenergic agonist) + 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor) and forskolin (diterpene). These agents promoted apoptosis (i.e., increased expression of annexin V) of wild-type (WT) S49 cells, but Bcl-2-overexpressing S49 cells were protected from this response. Bcl-2 overexpression did not protect cells from G(1) growth arrest but did allow cells to grow longer in culture and protected cells from culture-dependent necrosis. Commitment to and reversal from apoptosis vs. G(1) growth arrest by isoproterenol + 3-isobutyl-1-methylxanthine showed different kinetics. Although both processes required several hours to develop, removal of agonists readily reversed growth arrest, but not apoptosis. Thus commitment to apoptosis is less reversible than G(1) growth arrest. The findings also indicate that glucocorticoid- and cAMP-mediated G(1) growth arrest is unaffected by Bcl-2 overexpression, even though increased Bcl-2 allows these lymphoma cells to resist necrosis and apoptosis.
Zhang
L
L
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA.
Insel
P A
PA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D017304:Annexin A5 / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D019940:Genes, bcl-1; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008223:Lymphoma / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D017304:Annexin A5; D000893:Anti-Inflammatory Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D005576:Colforsin; D003907:Dexamethasone; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine