3-Hydroxykynurenine in Regulation of Drosophila Behavior: The Novel Mechanisms for Cardinal Phenotype Manifestations.

Autor:	Zhuravlev AV; Laboratory of Neurogenetics, Pavlov Institute of Physiology Russian Academy of Sciences, Saint Petersburg, Russia., Vetrovoy OV; Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology Russian Academy of Sciences, Saint Petersburg, Russia.; Department of Biochemistry, Faculty of Biology, Saint Petersburg State University, Saint Petersburg, Russia., Ivanova PN; Laboratory of Neurogenetics, Pavlov Institute of Physiology Russian Academy of Sciences, Saint Petersburg, Russia.; Department of Anatomy and Physiology of Humans and Animals, Faculty of Biology, Herzen State Pedagogical University of Russia, Saint Petersburg, Russia., Savvateeva-Popova EV; Laboratory of Neurogenetics, Pavlov Institute of Physiology Russian Academy of Sciences, Saint Petersburg, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2020 Aug 07; Vol. 11, pp. 971. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020).
DOI:	10.3389/fphys.2020.00971
Abstrakt:	Dysfunctions of kynurenine pathway of tryptophan metabolism (KPTM) are associated with multiple neuropathologies in vertebrates and invertebrates. Drosophila mutants with altered content of kynurenines are model objects for studying the molecular processes of neurodegeneration and senile dementia. The mutant cardinal ( cd 1 ) with accumulation of the redox stress inductor 3-hydroxykynurenine (3-HOK) shows age-dependent impairments of the courtship song and middle-term memory. The molecular mechanisms for 3-HOK accumulation in cd 1 are still unknown. Here, we have studied age-dependent differences in spontaneous locomotor activity (SLA) for the wild type strain Canton-S ( CS ), cd 1 , and cinnabar ( cn 1 ) with an excess of neuroprotective kynurenic acid (KYNA). We have also estimated the level and distribution of protein-bound 3-HOK (PB-3-HOK) in Drosophila brains (Br) and head tissues. The middle-age cd 1 show the higher running speed and lower run frequency compared to CS , for cn 1 the situation is the opposite. There is a decrease in the index of activity for 40-day-old cd 1 that seems to be an effect of the oxidative stress development. Surprisingly, PB-3-HOK level in Drosophila heads, brains, and head capsules (HC) is several times lower for cd 1 compared to CS . This complements the traditional hypothesis that cd 1 phenotype results from a mutation in phenoxazinone synthase (PHS) gene governing the brown eye pigment xanthommatin synthesis. In addition to 3-HOK dimerization, cd 1 mutation affects protein modification by 3-HOK. The accumulation of free 3-HOK in cd 1 may result from the impairment of 3-HOK conjugation with some proteins of the brain and head tissues. (Copyright © 2020 Zhuravlev, Vetrovoy, Ivanova and Savvateeva-Popova.)
Databáze:	MEDLINE
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