Control of oxidative stress resistance by IP3 kinase in Drosophila melanogaster.
Oxidative damage is thought to be a major causal factor of aging, and is implicated in several human pathologies such as Alzheimer's and Parkinson's diseases. Nevertheless the genetical determinants of in vivo oxidative stress response are still poorly understood. To identify cellular components whose deregulation leads to oxidative stress resistance, we performed a genetic screen in Drosophila melanogaster. We thus identified in this screen Drosophila Inositol 1,4,5-triphosphate kinase I (D-IP3K1), a Drosophila gene homologous to mammalian IP3Ks. In vertebrates, IP3Ks phosphorylate the second messenger Inositol 1,4,5-triphosphate (IP3) to produce Inositol 1,3,4,5 tetrakiphosphate (IP4). IP3 binding to its receptor (IP3R) triggers Ca(2+) release from the endoplasmic reticulum (ER) to the cytosol, whereas IP4 physiological role remains elusive. We show here that ubiquitous overexpression of D-IP3K1 confers resistance of flies to H(2)O(2)- but not to paraquat-induced oxidative stress. Additional genetic analysis with other members of IP3 and IP4 signaling pathways led us to propose that the D-IP3K1 protective effect is mainly mediated through the reduction of IP3 level (which probably results in reduced Ca(2+) release from internal stores), rather than through the rise of IP4 level.
Monnier
Véronique
V
Institut Jacques Monod, Université Paris, France.
Girardot
Fabrice
F
Audin
Wilfried
W
Tricoire
Hervé
H
D000818:Animals; D030801:Animals, Genetically Modified; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006540:Herbicides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction
D006540:Herbicides; D016877:Oxidants; D018160:Receptors, Cytoplasmic and Nuclear; C061107:inositol-1,3,4,5-tetrakisphosphate receptor; D015544:Inositol 1,4,5-Trisphosphate; D006861:Hydrogen Peroxide; D002374:Catalase; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010269:Paraquat; D002118:Calcium