Interactions between human immunodeficiency virus infection and hormonal pathways: enhancement of calcium-induced but reduction of glucocorticoid-induced cell death.
We examined the effect of chronic human immunodeficiency virus 1 (HIV-1) infection on the growth of human leukemic CEM T cells exposed to compounds which act through several major hormone or hormone-like signal transduction systems. Three were not altered by HIV-1 infection. Micromolar 8-bromo-cAMP inhibited cell growth equally in uninfected and infected cells. At the concentrations tested, neither (Bu)2cAMP nor the stimulator of protein kinase C, phorbol 12-myristate 13-acetate, altered the growth of infected or uninfected cells. The synthetic prostaglandin analog enisoprost also inhibited both equally. However, responses to two basic signal transduction systems, calcium uptake and the glucocorticoid pathway, were influenced by HIV infection. In chronically HIV-infected cells increased sensitivity to lysis by the calcium ionophore A23187 was observed. Additionally, the infected cells contained reduced amounts of glucocorticoid receptor sites and showed a statistically significant shift toward resistance to glucocorticoid-induced apoptosis.
University of Texas Medical Branch, Department of Human Biological Chemistry and Genetics, Galveston 77555-0645.
J S
JS
Smith
S
S
Kawa
M W
MW
Cloyd
E B
EB
Thompson
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007938:Leukemia; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D003994:Bucladesine; D003907:Dexamethasone; D011493:Protein Kinase C; D000527:Alprostadil; C054594:enisoprost; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium