Perturbations in Dopamine Synthesis Lead to Discrete Physiological Effects and Impact Oxidative Stress Response in Drosophila

The impact of mutations in four essential genes involved in dopamine (DA) synthesis and transport on longevity, motor behavior, and resistance to oxidative stress was monitored in Drosophila melanogaster. The fly lines used were: (i) a loss of function mutation in Catecholamines up (Catsup²⁶), (ii) a mutant for the gene pale (ple²), (iii) a mutant for the gene Punch (Pu^Z22), and (iv) a mutant in the vesicular monoamine transporter (VMAT^D14). Median lifespans of ple², Pu^Z22 and VMAT^D14 mutants were significantly decreased compared to Catsup²⁶ and wild type controls that did not significantly differ between each other. Catsup²⁶ flies survived longer when exposed to hydrogen peroxide (80 µM) or paraquat (10 mM) compared to ple², Pu^Z22 or VMAT^D14 and controls. These flies also exhibited significantly higher negative geotaxis activity compared to ple², Pu^Z22, VMAT^D14 and controls. Mutant flies demonstrated rhythmic circadian locomotor activity in general. Expression analysis of key antioxidant genes revealed that glutathione S-transferase Omega-1 (GSTO1) expression was significantly up-regulated in all DA synthesis pathway mutants and especially in Catsup²⁶ and VMAT^D14 flies at both mRNA and protein levels. Taken together, we hypothesize that DA could directly influence GSTO1 transcription and play a significant role in regulating the response of oxidative stress.