title: The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance.
abstract: There is a relationship between various cellular stress factors and aging. In earlier studies, we demonstrated that overexpression of the D-GADD45 gene increases the life span of Drosophila melanogaster. In this study, we investigate the relationship between D-GADD45 activity and resistance to oxidative, genotoxic and thermal stresses as well as starvation. In most cases, flies with constitutive and conditional D-GADD45 overexpression in the nervous system were more stress-resistant than ones without overexpression. At the same time, most of the studied stress factors increased D-GADD45 expression in the wild-type strain. The lifespan-extending effect of D-GADD45 overexpression was also retained after exposure to chronic and acute gamma-irradiation, with doses of 40 сGy and 30 Gy, respectively. However, knocking out D-GADD45 resulted in a significant reduction in lifespan, lack of radiation hormesis and radioadaptive response. A dramatic decrease in the spontaneous level of D-GADD45 expression was observed in the nervous system as age progressed, which may be one of the causes of the age-related deterioration of organismal stress resistance. Thus, D-GADD45 expression is activated by most of the studied stress factors, and D-GADD45 overexpression resulted in an increase of stress resistance.
authors.affiliation: Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology, Komi Science Center of Russian Academy of Sciences, Syktyvkar, Russia. amoskalev@ib.komisc.ru
authors.forename: Alexey
authors.initials: A
authors.lastname: Moskalev
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Plyusnina
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shaposhnikov
authors.forename: Lyubov
authors.initials: L
authors.lastname: Shilova
authors.forename: Alexey
authors.initials: A
authors.lastname: Kazachenok
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhavoronkov
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005720:Gamma Rays; D005838:Genotype; D006540:Herbicides / Q000633:toxicity*; D059165:Hormesis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008136:Longevity; D008297:Male; D009154:Mutation; D009420:Nervous System / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity; D013217:Starvation; D013696:Temperature; D000097642:GADD45 Proteins
chemical_list: D029721:Drosophila Proteins; D006540:Herbicides; D047908:Intracellular Signaling Peptides and Proteins; D010269:Paraquat; D000097642:GADD45 Proteins