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Regulation of human cytosolic sulfotransferases (SULTs) 1C2 and 1C3 by nuclear signaling pathways in LS180 cells
Author(s) -
Rondini Elizabeth Ann,
Fang Hailin,
RungeMorris Melissa,
Kocarek Thomas A.
Publication year - 2013
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.27.1_supplement.892.10
Subject(s) - calcitriol receptor , pregnane x receptor , nuclear receptor , activator (genetics) , transactivation , chemistry , liver x receptor , signal transduction , microbiology and biotechnology , gene expression , biology , transcription factor , receptor , gene , biochemistry
Enzymes of the SULT superfamily catalyze the sulfate conjugation of a myriad of endogenous and xenobiotic substrates. Among the human SULT families, little is known about regulation of the SULT1C enzymes. We evaluated the effects of a panel of nuclear signaling activators on levels of SULT mRNA (1C2 and 1C3) and protein (1C2) in LS180 colon cancer cells. Treatment with GW3965 (LXR activator), GW4064 (FXR), or rifampicin (PXR) significantly increased SULT1C2 and 1C3 mRNA levels. Vitamin D3 treatment (VDR) selectively increased SULT1C2 mRNA content, while TCDD (Ah receptor) or rosiglitazone (PPARγ) increased SULT1C3 mRNA levels. SULT1C2 protein levels were moderately increased by GW3965, GW4064, and rifampicin treatments and strongly increased (~5‐fold) by Vitamin D3. To evaluate SULT1C2 transcriptional regulation, treatment effects were determined on reporter expression from a transiently transfected plasmid containing ~5kb of the SULT1C2 gene, corresponding mainly to intron 1. Reporter activity was increased 2‐, 6‐, and 5‐fold by GW3965, GW4064, and Vitamin D3 treatment, respectively (P<0.05). These results indicate that SULT1C2 and 1C3 expression is regulated by several nuclear signaling pathways and suggest that regulatory elements for LXR, FXR, and VDR are contained within intron 1 of the SULT1C2 gene. This work was supported by NIH grants HL050710 and ES005823.