Differential Regulation of Bcl-xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid

Steve J. Morrissy, Haipeng Sun, Jack Zhang, Joshua Strom, Qin Chen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalJournal of Biochemical and Molecular Toxicology
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Corticosterone
Tretinoin
Gene expression
Progesterone
Transcription Factor AP-1
Gene Expression
NF-kappa B
Chemical activation
Messenger RNA
Cardiac Myocytes
Doxorubicin
Rats
Proteins
Genes
Binding Sites
Apoptosis

Keywords

  • Apoptosis
  • Cell Survival
  • Nuclear Receptor
  • Retinoids
  • Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Differential Regulation of Bcl-xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid. / Morrissy, Steve J.; Sun, Haipeng; Zhang, Jack; Strom, Joshua; Chen, Qin.

In: Journal of Biochemical and Molecular Toxicology, Vol. 30, No. 6, 01.06.2016, p. 309-316.

Research output: Contribution to journalArticle

Morrissy, Steve J. ; Sun, Haipeng ; Zhang, Jack ; Strom, Joshua ; Chen, Qin. / Differential Regulation of Bcl-xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid. In: Journal of Biochemical and Molecular Toxicology. 2016 ; Vol. 30, No. 6. pp. 309-316.
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