RRC ID 32505
Author Moskalev A, Plyusnina E, Shaposhnikov M, Shilova L, Kazachenok A, Zhavoronkov A.
Title The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance.
Journal Cell Cycle
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.
Volume 11(22)
Pages 4222-41
Published 2012-11-15
DOI 10.4161/cc.22545
PII 22545
PMID 23095639
PMC PMC3524218
MeSH Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism Drug Resistance Female Gamma Rays* Genotype Herbicides / toxicity* Hormesis Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Longevity Male Mutation Nervous System / metabolism Oxidative Stress / drug effects* Paraquat / toxicity Starvation Temperature
IF 3.259
Times Cited 12
Drosophila DGRC#112149