Activation of the promoters of genes associated with DNA damage, oxidativestress, ER stress and protein malfolding by the bile salt, deoxycholate

Toxic bile salts, retained within the liver because of impaired biliary exc retion, are considered to play a major role in liver injury during cholesta sis. Bile salts cause cellular stresses that may result in apoptosis. To be tter understand such cellular stresses, the effect of the bile salt sodium deoxycholate (NaDOC) on activation of 13 specific gene promoters or respons e elements associated with different cellular stresses was measured in the transformed human hepatoma line, HepG2. NaDOC was found to activate transcr iption factors and induce or activate the promoters of genes that respond t o protein malfolding (grp78 and hsp70), DNA damage (gadd153, hsp70 and c-fo s), oxidative stress (NF-kappa B, c-fos, hsp70 and gadd153), ER stress (grp 78) and Ca++ imbalance (grp78). (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.