Activation of the metallothionein IIA promoter and other key stress response elements by ursodeoxycholate in HepG2 cells: relevance to the cytoprotective function of ursodeoxycholate.
Ursodeoxycholate, used to treat a variety of pathologies, has the ability to reverse cytotoxic and hepatotoxic conditions. We examined HepG2, a hepatic cell line, treated with increasing levels of ursodeoxycholate, for responses of a range of promoters/response elements responsive to DNA damage, heavy metal ions, protein denaturants, aromatic hydrocarbons, retinoids, changes in intracellular AMP levels, end endoplasmic reticulum stress. The metallothionein IIA promoter was the most highly activated by ursodeoxycholate. Since ursodeoxycholate protects against the cytotoxic effects of deoxycholate, our data, combined with observations made by others, implicate metallothionein IIA as being important in this protective pathway.
Bernstein
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Department of Microbiology and Immunology, College of Medicine, Tucson, Ariz., 85724, USA. bernstein3@earthlink.net
Payne
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Bernstein
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Garewal
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D002470:Cell Survival / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008668:Metallothionein / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D011993:Recombinant Fusion Proteins; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D008668:Metallothionein; D015500:Chloramphenicol O-Acetyltransferase