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RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2002 Dec 10; Vol. 99 (25), pp. 16162-7. Date of Electronic Publication: 2002 Nov 27. - Publication Year :
- 2002
-
Abstract
- Oxidative stress has been widely implicated as an important factor in the aging process. Because mitochondrial respiration is the principal source of reactive oxygen within cells, the mitochondrially localized superoxide dismutase (SOD) 2 is thought to play an important front-line defensive role against aging-related oxidative stress. Although genetic studies with mutants deficient in SOD1, the predominantly cytosolic isoform of SOD, have been instrumental in elucidating the role of reactive oxygen metabolism in aging in Drosophila, the lack of available mutations in the Sod2 gene has hampered an equivalent analysis of the participation of this important antioxidant enzyme in the Drosophila aging model. Here we report that ablation of mitochondrial SOD2 through expression of a GAL4-regulated, inverted-repeat Sod2 RNA-interference transgene in an otherwise normal animal causes increased endogenous oxidative stress, resulting in loss of essential enzymatic components of the mitochondrial respiratory chain and the tricarboxylic acid cycle, enhances sensitivity to applied oxidative stress, and causes early-onset mortality in young adults. In sharp contrast, ablation of SOD2 has no overt effect on the development of larvae and pupae, which may reflect a fundamental transition in oxygen utilization andor reactive oxygen metabolism that occurs during metamorphosis from larval to adult life.
- Subjects :
- Animals
Citric Acid Cycle genetics
DNA-Binding Proteins
Drosophila Proteins genetics
Drosophila Proteins physiology
Drosophila melanogaster genetics
Drosophila melanogaster metabolism
Drug Resistance genetics
Electron Transport genetics
Iron-Sulfur Proteins deficiency
Isoenzymes deficiency
Isoenzymes genetics
Isoenzymes physiology
Longevity genetics
Oxidative Stress genetics
Paraquat toxicity
Promoter Regions, Genetic
Reactive Oxygen Species metabolism
Saccharomyces cerevisiae Proteins genetics
Superoxide Dismutase genetics
Superoxide Dismutase physiology
Transcription Factors genetics
Transgenes
Drosophila Proteins deficiency
Drosophila melanogaster enzymology
Mitochondria enzymology
RNA Interference
Superoxide Dismutase deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 99
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 12456885
- Full Text :
- https://doi.org/10.1073/pnas.252342899