title: Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells.
abstract: Retinoic acid (RA) induces apoptosis in Hep3B human hepatoma cells. 9-Cis-RA (c-RA) had a similar effect as all-trans-RA (t-RA) in inducing cell death in Hep3B cells. RA-induced Hep3B-cell death was associated with inhibited expression of the hepatocyte nuclear factor 4 (HNF-4) gene. Palmitoyl-CoA ((C16:0)-CoA), the reported HNF-4 ligand, prevented RA-induced apoptosis. The effect of (C16:0)-CoA was specific, since palmitic acid and co-enzyme A had no effect in preventing RA-induced apoptosis. Bovine serum albumin (BSA) also prevented RA-induced apoptosis. However, in contrast to BSA, which induced cell growth, (C16:0)-CoA alone had no effect on cell growth. Investigating the possible role of HNF-4 in apoptosis, the reported HNF-4 antagonist (C18:0)-CoA was employed, and it also prevented RA-induced apoptosis. By transient transfection, overexpression of HNF-4 did not prevent RA-induced apoptosis. The induction and prevention of apoptosis caused by RA and (C16:0)-CoA were associated, respectively with the induction and inhibition of the expression of transforming growth factor beta (TGFbeta), which is known to play a role in apoptosis. Furthermore, RA and (C16:0)-CoA can regulate AP-1, which is a key regulator of the TGFbeta gene. Our data indicate that fatty acyl-CoAs can prevent RA-induced apoptosis and that TGFbeta, rather than HNF-4, may play a role in these regulatory processes. Our data also suggest that (C16:0)-CoA and (C18:0)-CoA are not the agonist and antagonist for HNF4, respectively in the Hep3B cell system.
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA. sagrose@ucla.edu
authors.forename: Y J
authors.initials: YJ
authors.lastname: Wan
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: C
authors.initials: C
authors.lastname: Cowan
authors.forename: T R
authors.initials: TR
authors.lastname: Magee
mesh_terms: D000077556:Alitretinoin; D017209:Apoptosis / Q000187:drug effects*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005227:Fatty Acids / Q000494:pharmacology* / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology* / Q000502:physiology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D051557:Hepatocyte Nuclear Factor 4; D008024:Ligands; C403128:MLX protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D010171:Palmitoyl Coenzyme A; D000077556:Alitretinoin; D014212:Tretinoin