title: Differential Regulation of Bcl-xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid.
abstract: Corticosterone (CT), progesterone (PG), and retinoic acid (RA) are capable of inhibiting Doxorubicin (Dox) from inducing apoptosis in rat cardiomyocytes. Mechanistically, CT, PG, and RA induce increases of Bcl-xL protein and mRNA, and activate a 3.2 kb bcl-x gene promoter. CT and RA, but not PG, induced the activity of a 0.9 kb bcl-x promoter, containing sequences for AP-1 and NF-kB binding. RA, but not CT or PG, induced NF-kB activation. CT, but not PG or RA, induced AP-1 activation, and induction of the 0.9 kb bcl-x reporter by CT was inhibited by dominant negative c-Jun TAM-67 or removal of AP-1 binding site. Therefore, although CT, PG, and RA all induce Bcl-xL mRNA and protein, three independent mechanisms are in operation: while CT induces Bcl-xL via AP-1 transcription factor, and RA induces NF-kB activation and bcl-x promoter activity, PG induces Bcl-xL via a mechanism independent of NF-kB or AP-1.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Morrissy
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Strom
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA. qchen@email.arizona.edu.
authors.forename: Qin M
authors.initials: QM
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001665:Binding Sites; D003345:Corticosterone / Q000494:pharmacology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C494813:Bcl2l1 protein, rat; D016328:NF-kappa B; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C439528:TAM67 peptide; D018808:Transcription Factor AP-1; D051020:bcl-X Protein; D011374:Progesterone; D014212:Tretinoin; D004317:Doxorubicin; D008156:Luciferases; D003345:Corticosterone
keywords: Apoptosis; Cell Survival; Nuclear Receptor; Retinoids; Steroids