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《Glucocorticoid receptors are required for up-regulation of neuronal 5-lipoxygenase (5LOX) expression by dexamethasone.》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、TheFASEBJournalexpressarticle10.1096/fj.00-0836fje.PublishedonlineJune8,2001.Glucocorticoidreceptorsarerequiredforup-regulationofneuronal5-lipoxygenase(5LOX)expressionbydexamethasone†TolgaUz*,YogeshDwivedi*,AlbiQeli*,MarcPeters-Golden,GhanshyamPandey*,andHariManev
2、**ThePsychiatricInstitute,DepartmentofPsychiatry,CollegeofMedicine,UniversityofIllinois†atChicago,Chicago,Illinois;PulmonaryandCriticalCareMedicineDivision,DepartmentofInternalMedicine,UniversityofMichiganMedicalCenter,AnnArbor,MichiganCorrespondingauthor:HariMane
3、v,ThePsychiatricInstitute,TheUniversityofIllinoisatChicago,1601WestTaylorSt.,MC912,Chicago,IL60612.E-mail:HManev@psych.uic.eduABSTRACT5-lipoxygenase(5LOX)isthekeyenzymeinthesynthesisofleukotrienesfromarachidonicacid.Hyperglucocorticoidemia,dexamethasone,andagingup
4、-regulate5LOXinthebrain,includingthecerebelluminvivo.Westudiedthemechanismsofdexamethasone-triggered5LOXup-regulationinprimaryculturesofratcerebellargranuleneurons(CGN).Wemeasured5LOXmRNAandproteincontents,andtheformationofcysteinylleukotrienes(LTC4,LTD4,andLTE4
5、
mM)-increased5LOXmRNAandproteincontentswerealreadyobservedat3hoftreatment,andtheypersistedforatleast24h.Dexamethasonealso
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6、
imulatoryeffectofdexamethasoneon5LOXexpressionwasinhibitedbytheglucocorticoidreceptor(GR)antagonistRU486andbyreducingtheCGNcontentofGRreceptorproteinwithaGR-specificantisenseoligonucleotide.The5LOXmRNAhalf-lifewaslongerindexamethasonethaninvehicle-
7、treatedCGNs.Ourresultsindicatethatdexamethasoneincreases5LOXexpressioninCGNsinaGR-dependentmannerandthatitalsoincreasesthestabilityof5LOXmRNA.Furtherstudiesarewarrantedtoelucidatethephysiologic/pathologicsignificanceofglucocorticoid-regulatedexpressionof5LOXinthec
8、entralnervoussystem.Keywords:cerebellargranuleneurons·leukotrienes·arachidonicacid·cerebellargranuleneurons-Lipoxygenase(5LOX)enzymeactivityiscrucialfor
