Affiliation:
1. From the Center for Environmental and Rural Health, Texas A&M University, College Station, Tex.
Abstract
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
Cyp1al
and
Cyp1b1
is differentially influenced by Ahr phenotype and mitogenic status, with patterns that may dictate inherent susceptibility to atherogenic stimuli.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
93 articles.
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