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Article: Aldose reductase regulates hepatic peroxisome proliferator-activated receptor α phosphorylation and activity to impact lipid homeostasis

TitleAldose reductase regulates hepatic peroxisome proliferator-activated receptor α phosphorylation and activity to impact lipid homeostasis
Authors
Issue Date2008
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2008, v. 283 n. 25, p. 17175-17183 How to Cite?
AbstractAldose reductase (AR) is implicated in the development of a number of diabetic complications, but the underlying mechanisms remain to be fully elucidated. We performed this study to determine whether and how AR might influence hepatic peroxisome proliferator-activated receptor α (PPARα) activity and lipid metabolism. Our results in mouse hepatocyte AML12 cells show that AR overexpression caused strong suppression of PPARα/δ activity (74%, p < 0.001) together with significant down-regulation of mRNA expression for acetyl-CoA oxidase and carnitine palmitoyltransferase-1. These suppressive effects were attenuated by the selective AR inhibitor zopolrestat. Furthermore, AR overexpression greatly increased the levels of phosphorylated PPARα and ERK1/2. Moreover, AR-induced suppression of PPARα activity was attenuated by treatment with an inhibitor for ERK1/2 but not that for phosphoinositide 3-kinase, p38, or JNK. Importantly, similar effects were observed for cells exposed to 25 mM glucose. In streptozotocin-diabetic mice, AR inhibitor treatment or genetic deficiency of AR resulted in significant dephosphorylation of both PPARα and ERK1/2. With the dephosphorylation of PPARα, hepatic acetyl-CoA oxidase and apolipoprotein C-III mRNA expression was greatly affected and that was associated with substantial reductions in blood triglyceride and nonesterified fatty acid levels. These data indicate that AR plays an important role in the regulation of hepatic PPARα phosphorylation and activity and lipid homeostasis. A significant portion of the AR-induced modulation is achieved through ERK1/2 signaling. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/67827
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorQiu, Len_HK
dc.contributor.authorWu, Xen_HK
dc.contributor.authorChau, JFLen_HK
dc.contributor.authorSzeto, IYYen_HK
dc.contributor.authorWing, YTen_HK
dc.contributor.authorGuo, Zen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorOates, PJen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorYang, JYen_HK
dc.date.accessioned2010-09-06T05:58:37Z-
dc.date.available2010-09-06T05:58:37Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2008, v. 283 n. 25, p. 17175-17183en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67827-
dc.description.abstractAldose reductase (AR) is implicated in the development of a number of diabetic complications, but the underlying mechanisms remain to be fully elucidated. We performed this study to determine whether and how AR might influence hepatic peroxisome proliferator-activated receptor α (PPARα) activity and lipid metabolism. Our results in mouse hepatocyte AML12 cells show that AR overexpression caused strong suppression of PPARα/δ activity (74%, p < 0.001) together with significant down-regulation of mRNA expression for acetyl-CoA oxidase and carnitine palmitoyltransferase-1. These suppressive effects were attenuated by the selective AR inhibitor zopolrestat. Furthermore, AR overexpression greatly increased the levels of phosphorylated PPARα and ERK1/2. Moreover, AR-induced suppression of PPARα activity was attenuated by treatment with an inhibitor for ERK1/2 but not that for phosphoinositide 3-kinase, p38, or JNK. Importantly, similar effects were observed for cells exposed to 25 mM glucose. In streptozotocin-diabetic mice, AR inhibitor treatment or genetic deficiency of AR resulted in significant dephosphorylation of both PPARα and ERK1/2. With the dephosphorylation of PPARα, hepatic acetyl-CoA oxidase and apolipoprotein C-III mRNA expression was greatly affected and that was associated with substantial reductions in blood triglyceride and nonesterified fatty acid levels. These data indicate that AR plays an important role in the regulation of hepatic PPARα phosphorylation and activity and lipid homeostasis. A significant portion of the AR-induced modulation is achieved through ERK1/2 signaling. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.rightsThis research was originally published in [Journal Name]. Author(s). Title. Journal Name. Year. Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology-
dc.subject.meshAldehyde Reductase - metabolism-
dc.subject.meshGene Expression Regulation, Enzymologic-
dc.subject.meshLipids - chemistry-
dc.subject.meshLiver - metabolism-
dc.subject.meshPPAR alpha - metabolism-
dc.titleAldose reductase regulates hepatic peroxisome proliferator-activated receptor α phosphorylation and activity to impact lipid homeostasisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=283&issue=25&spage=17175&epage=17183&date=2008&atitle=Aldose+reductase+regulates+hepatic+peroxisome+proliferator-acactivated+receptor+alpha+phosphorylation+and+activity+to+impact+lipid+homeostasisen_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1074/jbc.M801791200en_HK
dc.identifier.pmid18445591-
dc.identifier.scopuseid_2-s2.0-47749155983en_HK
dc.identifier.hkuros182067en_HK
dc.identifier.hkuros144834-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47749155983&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume283en_HK
dc.identifier.issue25en_HK
dc.identifier.spage17175en_HK
dc.identifier.epage17183en_HK
dc.identifier.isiWOS:000256720600026-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridQiu, L=24475532300en_HK
dc.identifier.scopusauthoridWu, X=7407060267en_HK
dc.identifier.scopusauthoridChau, JFL=9236841800en_HK
dc.identifier.scopusauthoridSzeto, IYY=6602491785en_HK
dc.identifier.scopusauthoridWing, YT=25937059500en_HK
dc.identifier.scopusauthoridGuo, Z=7404658072en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridOates, PJ=7004883807en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridYang, JY=8915077600en_HK

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