distinct mechanisms underlying tolerance to intermittent and constant hypoxia in drosophila melanogaster不同的机制宽容在黑腹果蝇间歇和持续缺氧.pdfVIP

Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster 1 1 1 1,2,3 Priti Azad , Dan Zhou , Erilynn Russo , Gabriel G. Haddad * 1 Department of Pediatrics, Section of Respiratory Medicine, University of California San Diego, La Jolla, California, United States of America, 2 Department of Neuroscience, University of California San Diego, La Jolla, California, United States of America, 3 The 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 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% O2) intermittent or constant hypoxia. Methodology/Principal Findings: 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