title: Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.
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 injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O(2)) intermittent or constant hypoxia.
  
  
  RESULTS
  Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia 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-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies.
  
  
  CONCLUSIONS
  We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival.
authors.affiliation: Department of Pediatrics, Section of Respiratory Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Priti
authors.initials: P
authors.lastname: Azad
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Erilynn
authors.initials: E
authors.lastname: Russo
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D019450:Genes, MDR; D049750:Genome, Insect; D055106:Genome-Wide Association Study; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D017931:DNA Primers; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C105998:Hsp23 protein, Drosophila; D012333:RNA, Messenger; D027981:Symporters; C069935:mdr49 protein, Drosophila; D010088:Oxidoreductases