title: Acetaldehyde alters MAP kinase signalling and epigenetic histone modifications in hepatocytes.
abstract: Although both oxidative and non-oxidative metabolites of ethanol are involved in generating ethanol matabolic stress (Emess), the oxidative metabolite acetaldehyde plays a critical role in the cellular actions of ethanol. We have investigated the effects of acetaldehyde on p42/44 MAP kinase, p46/p54 c-jun N-terminal kinase (JNK1/JNK2) and p38 MAP kinase in hepatocytes. Acetaldehyde caused temporal activation of p42/44 MAPK followed by JNK, but the activation of the p42/44 MAPK was not a prerequisite for the JNK activation. Activation ofJNK1 by acetaldehyde was greater than JNK2. Ethanol and acetaldehyde activatedJNK have opposing roles; ethanol-induced JNK activation increased apoptosis whereas that by acetaldehyde decreased apoptosis. Acetaldehyde also caused histone H3 acetylation at Lys9 and phosphorylation of histone H3 at Serl0 and 28, the latter being dependent on p38 MAP kinase. Phosphorylation at Ser28 was higher than at Serl0. Thus acetaldehyde distinctively alters MAP kinase signalling and histone modifications, processes involved in transcriptional activation.
authors.affiliation: Department of Medical Pharmacology & Physiology, University of Missouri School of Medine, Columbia, MO 65212, USA.
authors.forename: Shivendra D
authors.initials: SD
authors.lastname: Shukla
authors.forename: Youn Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Pil-hoon
authors.initials: PH
authors.lastname: Park
authors.forename: Annayya R
authors.initials: AR
authors.lastname: Aroor
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D006657:Histones; D000431:Ethanol; D020928:Mitogen-Activated Protein Kinases; D000079:Acetaldehyde