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Pages
- Title
- Methionine sulfoxide reductase (MSR) modulates lifespan andLocomotion in drosophila melanogaster.
- Creator
- Bruce, Lindsay, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Oxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in...
Show moreOxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in proteins back to methionine. This study, using Drosophila melanogaster, decribes the first animal system lacking both MsrA and MsrB. The loss of either MsrA or MsrB had no effect on lifespan in Drosophila, but loss of MsrB results in a slight decrease in locomotor activity from middle age onward. Double mutants lacking both forms of Msr have a significantly decreased lifespan and decreased locomotor activity at all ages examined. The double Msr mutants had no detectable increase in protein oxidation or decrease in mitochondrial function and were not more sensitive to oxidative stress. These results suggested that other cellular antioxidant systems were protecting the flies against oxidative damage and the decreased life span observed in the double knockouts was not due to widespread oxidative damage. However, one cannot exclude limited oxidative damage to a specific locus or cell type. In this regard, it was observed that older animals, lacking both MsrA and MsrB, have significantly reduced levels of dopamine, suggesting there might be oxidative damage to the dopaminergic neurons. Preliminary results also suggest that the ratio of F to G actin is skewed towards G actin in all mutants. The present results could have relevance to the loss of dopaminergic neurons in Parkinson’s disease.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004431, http://purl.flvc.org/fau/fd/FA00004431
- Subject Headings
- Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress, Proteins -- Chemical modification
- Format
- Document (PDF)
- Title
- Methionine sulfoxide reductase (Msr) deficiency leads to a reduction of dopamine levels in Drosophila.
- Creator
- Hernandez, Caesar, Binninger, David, Weissbach, Herbert, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Biological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological...
Show moreBiological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological disorders including the loss of fine motor control—a neurodegenerative condition characteristic of Parkinson’s disease (PD). We found that dopamine levels in the heads of MsrAΔ/ΔBΔ/Δ mutants are significantly reduced in comparison to MsrA ⁺/⁺ B⁺/⁺ heads. In addition, wefound protein and expression levels are markedly reduced in an Msr-deficient system. Our findings suggest an important role for the Msr system in the CNS.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004202, http://purl.flvc.org/fau/fd/FA00004202
- Subject Headings
- Cellular signal transduction, Dopamine -- Receptors, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Proteins -- Chemical modification
- Format
- Document (PDF)
