Analysis of drosophila stress resistance at pharmacological inhibition of prostaglandins metabolism
Abstract
Inhibition of inflammatory processes in the model organisms using non-steroidal anti-inflammatory drugs (NSAIDs) can be an effective geroprotective method. The mechanisms of NSAIDs action in insects have not been studied enough. It is assumed that they are similar to those in mammals and are based on the inhibition of cyclooxygenase 2, which leads to a decrease in the synthesis of prostaglandins. Prostaglandins are central signaling molecules for mediated coordinated cellular immunity of insects and control the imago eclosion, egg production and oogenesis of Drosophila. Obviously, signaling pathways exist where the role of prostaglandins has not yet been shown. In our work, the resistance to starvation of Drosophila melanogaster of wild type stock Canton-S under pharmacological inhibition of prostaglandin metabolism at different stages of ontogenesis was analyzed. In the experiments, nimesulide was used in three different concentrations – 0.1, 0.05, and 0.025 mg/ml. The results of the experiments have shown, that the development of larvae in the medium containing NSAID nimesulide leads to a decrease in resistance to stress factor – starvation on average by 19.2% in females and by 7.4% in males. Resistance to starvation of the most stress-resistant (10% of individuals with the longest life span) females decreases during the development of larvae in the medium containing nimesulide in concentrations 0.1 and 0.05 mg/ml. The consumption of nimesulide by imago at a concentration of 0.025 mg/ml during the first days of life increases stress resistance and life span at starvation in females by 12.4% and in males in all variants of the experiment on average by 17.8%. Under the same experimental conditions, life span during starvation increased in the most stress-resistant females Canton-S. Thus, pharmacological inhibition of prostaglandin metabolism leads to an increase of resistance to starvation if virgin adults are exposed to nimesulide during the first day after eclosion, and stress resistance decreases if nimesulide is consumed by larvae. This is obviously, due to that somatic tissues of the adult flies are almost entirely composed of postmitotic cells, while intensive processes of cell division are characteristic of growing larvae. The data obtained indicate that the action of nimesulide on postmitotic imago cells promotes transition of cells to increased stress tolerance, while the impact on actively dividing cells of larvae leads to a decrease in the resistance of the adults.
Downloads
References
Гланц С. Медико-биологическая статистика. – Москва: Практика, 1998. – С. 386–394. /Glantz S. Primer of biostatistics. – Мoscow: Praktika, 1998. – P. 386–394./
Рощупкин А.А. Некоторые критерии фармакологической геропротекции // Український журнал клiнiчної та лабораторної медицини. – 2013. – Т.8, №4. – С. 32–35. /Roshchupkin A.A. Some criteria of pharmacological geroprotection // Ukrainian Journal of Clinical and Laboratory Medicine. – 2013. – Vol.8, no. 4. – P. 32–35./
Фролькис В.В. Старение и увеличение продолжительности жизни. – Ленинград: Наука, 1988. – 239с. /Frolkis V.V. Aging and increase of life span. – Leningrad: Nauka, 1988. – 239р./
Ahmed S., Stanley D., Kim Y. An insect prostaglandin E2 synthase acts in immunity and reproduction // Front. Physiol. – 2018. – Vol.4 (9). – Article 1231.
Anisimov V.N. Rodent models for the preclinical evaluation of drugs suitable for pharmacological intervention in aging // Expert Opin. Drug Discov. – 2012. – Vol.7 (1). – P. 85–95.
Bharathi S.N., Prasad N.G., Shakarad M. et al. Variation in adult life history and stress resistance across five species of Drosophila // J. Genet. – 2003. – Vol.82, no. 3. – P. 191–205.
Ching T.T., Chiang W.C., Chen C.S. et al. Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity // Aging Cell. – 2011. – Vol.10, no. 3. – P. 506–519.
Choi S.H., Aid S., Caracciolo L. et al. Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer’s disease // J. Neurochem. – 2013. – Vol.124. – P. 59–68.
Danilov A., Shaposhnikov M., Shevchenko O. et al. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity // Oncotarget. – 2015. – Vol.6. – P. 19428–19444.
David S., Haas E., Miller J. Eicosanoids: Exploiting Insect Immunity to Improve Biological Control Programs // Insects. – 2012. – Vol.3 (2). – Р. 492–510.
Franceschi C., Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases // J. Gerontol. A Biol. Sci. Med. Sci. – 2014. – Vol.69 (1). – S4–S9.
Harbison S.T., Chang S., Kamdar K.P. et al. Quantitative genomics of starvation stress resistance in Drosophila // Genome Biol. – 2005. – Vol.6. – P. 30–36.
He C., Tsuchiyama S.K., Nguyen Q.T. et al. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import // PLoS Genet. – 2014. – Vol.10. –e1004860.
Kenyon C. A pathway that links reproductive status to lifespan in Caenorhabditis elegans // Ann. N. Y. Acad. Sci. – 2010. – Vol.1204. – P. 156–162.
Marron M.T., Markow T.A., Kain K.J. et al. Effects of starvation and desiccation on energy metabolism in desert and mesic Drosophila // J. Insect Physiol. – 2003. – Vol.49, no. 3. – P. 261–270.
Mattson С. Age, cell and adaptability // Aging Cell. – 2006. – Vol.6. – P. 112–134.
Moskalev A., Chernyagina E., de Magalhães J.P. et al. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease // Aging (Albany NY). – 2015. – Vol. 7 (9). – P. 616–628.
Poole J.C., Thain A., Perkins N.D. et al. Induction of transcription by p21Waf1/Cip1/Sdi1: role of NFkappaB and effect of non-steroidal anti-inflammatory drugs // Cell Cycle. – 2004. – Vol.3. – P. 931–940.
Prasad N.G., Dey S., Shakarad M., Amitabh J. The evolution of population stability as a by-product of life-history evolution // Proc. R. Soc. Lond. B. Biol. Sci. – 2003. – Vol.270. – P. 84–86.
Proshkina E., Lashmanova E., Dobrovolskaya E. et al. Geroprotective and radioprotective activity of quercetin, (-)-epicatechin, and ibuprofen in Drosophila melanogaster // Front. Pharmacol. – 2016. – Vol.7. – Article 505.
Rauschenbach I.Y., Shumnaya L.V., Khlebodarova T.M. et al. Role of phenol oxidases and tyrosine hydroxylase in control of dopamine content in Drosophila virilis under normal conditions and heat stress // J. Insect Physiol. – 2005. – Vol.41. – P. 279–286.
Service P. The effect of mating status on life-span, egg laying, and starvation resistance in Drosophila melanogaster in relation to selection on longevity // J. Insect. Physiol. – 1989. – Vol.35. – P. 447–452.
Simon A. Steroid control of longevity in Drosophila melanogaster // Science. – 2003. – Vol.299. – P. 1407–1410.
Strong R. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice // Aging Cell. – 2008. – Vol.7. – P. 641–650.
Tootle T.L., Spradling A.C. Drosophila Pxt: a cyclooxygenase-like facilitator of follicle maturation // Development (Cambridge, England). – 2008. – Vol.135 (5). – P. 839–847.
Vanaja K., Wahl M.A., Bukarica L. et al. Liposomes as carriers of the lipid soluble antioxidant resveratrol: evaluation of amelioration of oxidative stress by additional antioxidant vitamin // Life Sci. – 2013. – Vol.93, no. 24. – P. 917–923.
Zwaan В. Starvation resistance and longevity in Drosophila melanogaster in relation to pre-adult breeding conditions // Heredity. – 1991. – Vol.66. – P. 29–39.
Authors retain copyright of their work and grant the journal the right of its first publication under the terms of the Creative Commons Attribution License 4.0 International (CC BY 4.0), that allows others to share the work with an acknowledgement of the work's authorship.
