Constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells: Role of the Ahr bHLH/PAS transcription factor

J. Kevin Kerzee, Kenneth S. Ramos

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Ahr is a ligand-activated bHLH/PAS transcription factor involved in cytochrome P450 (CYP) gene regulation and murine susceptibility to atherogenic stimuli. The present studies were conducted to examine constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells (VSMCs) from Ahr+/+ and Ahr-/- mice. Cyp1a1 mRNA was not expressed constitutively in VSMCs irrespective of Ahr phenotype. Although Cyp1a1 was inducible in Ahr+/+ by 3 μmol/L benzo(a)pyrene, a known hydrocarbon inducer, the protein was uninducible. In contrast, Cyp1b1 mRNA and protein were expressed under constitutive and inducible conditions irrespective of Ahr phenotype or growth status. CYP-encoded aryl hydrocarbon hydroxylase activity was higher in Ahr-/- VSMCs under constitutive conditions and induced by benzo(a)pyrene in Ahr+/+ and Ahr-/- VSMCs. CYP expression was influenced by mitogenic status, because randomly cycling cells consistently exhibited higher levels than growth-arrested counterparts. Actinomycin D (2 μg/mL) or cycloheximide (10 μmol/L) did not inhibit constitutive or hydrocarbon-inducible aryl hydrocarbon hydroxylase activity in VSMCs. These data indicate that in murine VSMCs, expression of Cyp1a1 and Cyp1b1 is differentially influenced by Ahr phenotype and mitogenic status, with patterns that may dictate inherent susceptibility to atherogenic stimuli.

Original languageEnglish (US)
Pages (from-to)573-582
Number of pages10
JournalCirculation research
Volume89
Issue number7
DOIs
StatePublished - Sep 28 2001

Keywords

  • Aryl hydrocarbon receptor
  • Atherogenesis
  • Cyp1a1
  • Cyp1b1
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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