Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate.
Toxic bile salts, retained within the liver because of impaired biliary excretion, are considered to play a major role in liver injury during cholestasis. Bile salts cause cellular stresses that may result in apoptosis. To better understand such cellular stresses, the effect of the bile salt sodium deoxycholate (NaDOC) on activation of 13 specific gene promoters or response elements associated with different cellular stresses was measured in the transformed human hepatoma line, HepG2. NaDOC was found to activate transcription factors and induce or activate the promoters of genes that respond to protein malfolding (grp78 and hsp70), DNA damage (gadd153, hsp70 and c-fos), oxidative stress (NF-kappaB, c-fos, hsp70 and gadd153), ER stress (grp78) and Ca++ imbalance (grp78).
Bernstein
H
H
Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson 85724, USA.
Payne
C M
CM
Bernstein
C
C
Schneider
J
J
Beard
S E
SE
Crowley
C L
CL
D001647:Bile Acids and Salts / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival; D004249:DNA Damage / Q000235:genetics; D011088:DNA Ligases / Q000235:genetics; D003840:Deoxycholic Acid / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D014162:Transfection; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D003840:Deoxycholic Acid; D011088:DNA Ligases