title: Knockdown of adipokinetic hormone synthesis increases susceptibility to oxidative stress in Drosophila--a role for dFoxO?
abstract: Insect adipokinetic hormones (AKHs) are pleiotropic hormones known to play a protective role in response to oxidative stress (OS). However, the precise signaling pathways are unclear. We present evidence that AKH may primarily employ the Forkhead box class O transcription factor (FoxO) to exert this effect. The impact of knocking down AKH synthesis or its over-expression in its response to OS was studied in Drosophila melanogaster. AKH knockdown (AKH-RNAi) as well as AKH overexpression (AKH-oex) was achieved using the Gal-4/UAS system and controls were w(1118) (+/+), AKH-Gal4/+, UAS-AKH/+ and UAS-AKH-RNAi/+. Exposure to 80 μM hydrogen peroxide (HP) revealed that AKH-RNAi flies showed significantly higher mortality than AKH-oex or the respective control lines. This susceptibility was evidenced by significantly enhanced levels of protein carbonyls - a biomarker of OS, in AKH-RNAi flies compared to controls and AKH-oex flies. Interestingly, AKH-oex flies had the least amount of protein carbonyls. AKH-RNAi flies had significantly less dFoxO transcript and translated protein compared to control and AKH-oex flies in un-challenged condition as well as when challenged with HP. Sestrin - a major antioxidant defense protein and one of the targets of dFoxO - was also significantly down-regulated (both at mRNA and protein level) in AKH-RNAi flies (both unchallenged and challenged with HP) compared to control flies and flies with over-expressed AKH. These findings imply that dFoxO may act downstream of AKH as a transcription factor to mediate response to OS in D. melanogaster.
authors: Institute of Entomology, Biology Centre, Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic; Faculty of Science, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA.
authors: Andrea
authors: A
authors: Bednářová
authors: Institute of Entomology, Biology Centre, Academy of Sciences, Branišovská 31, 370 05 České Budějovice, Czech Republic; Faculty of Science, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic.
authors: Dalibor
authors: D
authors: Kodrík
authors: Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Electronic address: nk260@msstate.edu.
authors: Natraj
authors: N
authors: Krishnan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004351:Drug Resistance; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007301:Insect Hormones / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D050050:Protein Carbonylation / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D007301:Insect Hormones; D009842:Oligopeptides; D016877:Oxidants; D012333:RNA, Messenger; D011994:Recombinant Proteins; C065368:DAKH peptide; D006861:Hydrogen Peroxide; D011761:Pyrrolidonecarboxylic Acid
keywords: Adipokinetic hormone; Drosophila; FoxO; Hydrogen peroxide; Oxidative stress