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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#_5 http://www.w3.org/ns/prov#value BACKGROUND: The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat-1 (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression. METHODS: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter-reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPARalpha on the expression of ALDH2 by using PPARalpha-null mice. RESULTS: In vitro translated PPARs bound the ALDH NRRE with high affinity. Mutation of the NRRE indicated that binding was mediated by the DR-1 element. Cotransfection of PPAR expression plasmids showed that PPARalpha had no effect on expression of heterologous promoter constructs containing the NRRE. PPARgamma slightly induced expression, whereas PPARdelta repressed basal activity of the promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either stock rodent chow or a low-protein diet. Consistent with the transfection data, expression of ALDH2 protein was not different in PPARalpha-null mice. Treatment of the mice with the PPARalpha agonist WY14643 slightly decreased the level of ALDH2 protein in both wild-type and PPARalpha-null mice, suggesting that the effect of WY14643 was not mediated by the receptor. CONCLUSIONS: These data indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and proteins regulated by PPARalpha http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11505017 http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11505017 http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#_5 http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ#pubinfo http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ http://purl.org/dc/terms/created 2014-07-03T14:29:57.851+02:00 http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAgD9y5CuwZowGU7yjyUopgC0ze_4_W7c1fNjbyVvTDtQ http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234