Perturbations in dopamine synthesis lead to discrete physiological effects and impact oxidative stress response in Drosophila

作者: Marley E. Hanna , Andrea Bednářová , Kuntol Rakshit , Anathbandhu Chaudhuri , Janis M. O’Donnell

DOI: 10.1016/J.JINSPHYS.2015.01.001

关键词: Wild typeMutantOxidative stressBiologyVesicular monoamine transporterGlutathioneCell biologyBiochemistryDrosophila melanogasterTyrosine hydroxylaseDopamine

摘要: The impact of mutations in four essential genes involved dopamine (DA) synthesis and transport on longevity, motor behavior, resistance to oxidative stress was monitored Drosophila melanogaster. fly lines used for this study were: (i) a loss function mutation Catecholamines up (Catsup26), which is negative regulator the rate limiting enzyme DA synthesis, (ii) mutant gene pale (ple2) that encodes tyrosine hydroxylase (TH), (iii) Punch (PuZ22) guanosine triphosphate cyclohydrolase, required TH activity, (iv) vesicular monoamine transporter (VMATΔ14), packaging as vesicles inside neurons. Median lifespans ple2, PuZ22 VMATΔ14 mutants were significantly decreased compared Catsup26 wild type controls did not differ between each other. flies survived longer when exposed hydrogen peroxide (80 μM) or paraquat (10 mM) controls. These also exhibited higher geotaxis activity PuZ22, All demonstrated rhythmic circadian locomotor general, albeit had slightly weaker rhythms. Expression analysis some key antioxidant revealed glutathione S-transferase Omega-1 (GSTO1) expression up-regulated all pathway especially at both mRNA protein levels. Taken together, we hypothesize could directly influence GSTO1 transcription thus play significant role regulation response stress. Additionally, perturbations do appear have rhythms per se, but an general

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