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Regulation of SULT1C2 expression by endogenous isoprenoids in primary cultured rat hepatocytes
Author(s) -
Duniec-Dmuchowski Zofia,
Dombkowski Alan A.,
Kocarek Thomas A.,
Runge-Morris Melissa
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.673.11
Subject(s) - pravastatin , endogeny , reductase , mevalonate pathway , hmg coa reductase , messenger rna , activator (genetics) , constitutive androstane receptor , hydroxymethylglutaryl coa reductase , biology , chemistry , phenobarbital , enzyme , biochemistry , endocrinology , nuclear receptor , receptor , cholesterol , transcription factor , gene
SULT1C2 is a cytosolic sulfotransferase that catalyzes the bioactivation of arylamines. However, little is known about the mechanisms regulating expression of this enzyme. Treatment of primary cultured rodent hepatocytes with the squalene synthase inhibitor, squalestatin 1, increases CYP2B expression by causing accumulation of an endogenous isoprenoid that activates the constitutive androstane receptor (CAR). Treatment of primary cultured rat hepatocytes with 0.1 μM squalestatin 1 for 48 hr increased SULT1C2 mRNA content by ~3‐fold, as indicated by microarray and real‐time RT‐PCR analyses. Real‐time RT‐PCR also demonstrated that treatment of primary cultured rat hepatocytes with the HMG‐CoA reductase inhibitor, pravastatin (30 μM), decreased SULT1C2 mRNA content by ~50% while treatment with the HMG‐CoA reductase product, mevalonate (10 mM), increased the SULT1C2 mRNA level by ~3‐fold. Also, pravastatin treatment abolished squalestatin 1‐mediated SULT1C2 induction, while mevalonate supplementation restored induction. Treatment of primary cultured rat hepatocytes with the prototypic CAR activator, phenobarbital (100 μM), had no effect on SULT1C2 expression. These results indicate that SULT1C2 expression is regulated by one or more endogenous isoprenoids and suggest that this regulation is not mediated through CAR. Supported by NIH grants HL050710 and ES005823.