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Age-associated oxidative damage leads to absence of γ-cystathionase in over 50% of rat lenses: Relevance in cataractogenesis
- Source :
- Free Radical Biology and Medicine. 38:575-582
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Oxidative damage to lens proteins and glutathione depletion play a major role in the development of senile cataract. We previously found that a deficiency in gamma-cystathionase activity may be responsible for glutathione depletion in old lenses. The aims of this study were: (1) to investigate the mechanism that causes the age-related deficiency in gamma-cystathionase activity in the eye lens, and (2) to determine the role of gamma-cystathionase deficiency in cataractogenesis. Two populations of old rats were found, one (56%) whose lenses lacked gamma-cystathionase activity and the rest that exhibited detectable enzyme activity. gamma-Cystathionase protein was absent in lenses from old rats without gamma-cystathionase activity. Oxidative stress targeted gamma-cystathionase in the eye lens upon aging, since the enzyme contained more carbonyl groups in old lenses than in young ones. gamma-Cystathionase mRNA was also markedly reduced in old lenses, thus contributing to the age-associated deficiency in gamma-cystathionase. Inhibition of gamma-cystathionase activity caused glutathione depletion in lenses and led to cataractogenesis in vitro. In conclusion, the lack of gamma-cystathionase activity in over 50% of old lenses is due to decreased gene expression and proteolytic degradation of the oxidized enzyme. This results in a high risk for the development of senile cataract.
- Subjects :
- Aging
medicine.medical_specialty
genetic structures
Glycine
medicine.disease_cause
Biochemistry
Cataract
Lens protein
chemistry.chemical_compound
Physiology (medical)
Internal medicine
Lens, Crystalline
Gene expression
medicine
Animals
Rats, Wistar
Glyceraldehyde 3-phosphate dehydrogenase
chemistry.chemical_classification
biology
Cystathionine gamma-lyase
Cystathionine gamma-Lyase
Glutathione
eye diseases
Enzyme assay
Rats
Oxidative Stress
Endocrinology
Enzyme
chemistry
Alkynes
biology.protein
sense organs
Oxidative stress
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....9b260f1ba84006b3ac8af4c729784c90