The inhibition of superoxide production in EL4 lymphoma cells overexpressing growth hormone.
A substantial body of research exists to support the production of growth hormone by cells of the immune system. However, the function and mechanism of action of lymphocyte-derived growth hormone remain largely unelucidated. Since, it has been found that exogenous growth hormone (GH) primes neutrophils for the production of reactive oxygen intermediates (ROI) and in particular superoxide (O2-), we investigated the role of GH on the production of O2- in T cells. Furthermore, we examined whether endogenous and exogenous GH act similarly. Our studies show that overexpression of GH in EL4, a T-cell lymphoma cell line, results in a decrease in the production of O2- compared to control cells, as detected using the fluorescent dye, dihydroethidium. O2- production in control cells was not affected by treatment with inhibitors of xanthine oxidase or a non-specific NADPH-oxidase inhibitor. However, treatment with diallyl sulfide, an inhibitor of cytochrome P450 2E1 mimicked the reduction in O2- production seen in cells overexpressing GH. Although no significant change could be detected in CYP2E1 protein levels, CYP2E1 activity was found to be greater in control EL4 than in cells overexpressing GH. Both the decrease in O2- production and the lower CYP2E1 activity in GH overexpressing cells could be abrogated by treatment with N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase. The overexpression of GH protects cells from apoptosis induced by isoniazid, a CYP2E1 inducer, suggesting a role for nitric oxide as a mediator in the regulation of xenobiotic metabolism and apoptosis-protection by lymphocyte GH.
Arnold
Robyn E
RE
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Weigent
Douglas A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005470:Fluorometry; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D007538:Isoniazid / Q000494:pharmacology; D016399:Lymphoma, T-Cell / Q000473:pathology; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D013481:Superoxides; D019323:omega-N-Methylarginine; D013006:Growth Hormone; D019392:Cytochrome P-450 CYP2E1; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D007538:Isoniazid