title: Adrenocorticotropin induces heme oxygenase-1 expression in adrenal cells.
abstract: Heme oxygenase (HO) catalyzes the first and rate-controlling step of heme catabolism into biliverdin, iron and carbon monoxide. Three isoforms of HO have been identified so far: the inducible HO-1 and the constitutive HO-2 and HO-3. Both HO-1 and HO-2 were expressed in zona fasciculata (ZF) adrenal cells and in a mouse adrenocortical cell line (Y1). HO-1 but not HO-2 expression was upregulated by adrenocorticotropic hormone (ACTH) and accumulation of HO-1 protein correlated with an increase in HO activity in Y1 cells. ACTH induced HO-1 expression in a time- and dose-dependent manner with a maximum after 5 h of treatment and a threshold concentration of 0.1 mIU/ml. Actinomycin D and cycloheximide completely blocked the effect of ACTH on HO-1 mRNA expression whereas mRNA stability was not affected by ACTH. Permeable analogs of cAMP mimicked the effect of ACTH on HO-1 expression and ACTH induction was prevented by the protein kinase A (PKA) inhibitor H89. Steroid production was significantly increased when both HO-1 and HO-2 activities were inhibited by Sn-protoporphyrin IX (SnPPIX). The lipid peroxidation and increase in carbonyl content triggered by hydrogen peroxide was prevented by treatment of Y1 cells with bilirubin and ACTH.
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5 piso, C1121 ABG, Buenos Aires, Argentina.
authors.forename: Y
authors.initials: Y
authors.lastname: Pomeraniec
authors.forename: N
authors.initials: N
authors.lastname: Grion
authors.forename: L
authors.initials: L
authors.lastname: Gadda
authors.forename: V
authors.initials: V
authors.lastname: Pannunzio
authors.forename: E J
authors.initials: EJ
authors.lastname: Podesta
authors.forename: C B
authors.initials: CB
authors.lastname: Cymeryng
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007546:Isoquinolines / Q000494:pharmacology; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D011284:Pregnenolone / Q000032:analysis; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013268:Stimulation, Chemical; D013449:Sulfonamides; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; D013449:Sulfonamides; D017392:Thiobarbituric Acid Reactive Substances; D003609:Dactinomycin; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C105245:heme oxygenase-2; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D001663:Bilirubin