Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster 英文参考文献.docVIP

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Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster 英文参考文献.doc

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Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster 英文参考文献

DistinctMechanismsUnderlyingToleranceto IntermittentandConstantHypoxiainDrosophila melanogaster PritiAzad1,DanZhou1,ErilynnRusso1,GabrielG.Haddad1,2,3* 1Department of Pediatrics, Section of Respiratory Medicine, University of California San Diego, La Jolla, California, United States of America, 2Department of Neuroscience, University of California San Diego, La Jolla, California, United States of America, 3The Rady Children’s Hospital, San Diego, California, United States of America Abstract Background: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injuryoradaptationtohypoxicstressusingDrosophilaasamodelsystem.Ourcurrentgenome-widestudyisdesignedto investigategeneexpressionchangesandidentifyprotectivemechanism(s)inD.melanogasterafterexposuretosevere(1% O2)intermittentorconstanthypoxia. Methodology/Principal Findings: Our microarray analysis has identified multiple gene families that are up- or down- regulatedinresponsetoacuteCHorIH.WeobserveddistinctresponsestoIHandCHingeneexpressionthatvariedinthe numberofgenesandtypeofgenefamilies.Wethenstudiedtheroleofcandidategenes(up-ordown-regulated)inhypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up- regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P- elementlinesduringCH.Incontrast,duringIHtreatmenttheup-regulationofMdr49andl(2)08717genes(P-elementlines) providedsurvivaladvantageovercontrols.Thissuggeststhattheincreasedtranscriptlevelsfollowingtreatmentwitheither paradigmplayanimportantroleintolerancetoseverehypoxia.Furthermore,byover-expressingHsp70inspecifictissues, wefoundthatup-regulationofHsp70inheartandbrainplaycriticalroleintolerancetoCHinflies. Conclusions/Significance:Weobservedthatthegeneexpressionrespo