Inflammatory Response and Oxidative Stress in the Degeneration of Dopamine Neurons in Parkinson's Disease
Abstract
The experiments performed during the second grant period were designed to investigate the role of arachidonic acid (AA) release and metabolism in the toxicity caused by the depletion of GSH in primary mesencephalic cultures. Our experiments demonstrated that: (1) Inhibition of phospholipase A2, which decreases AA release, and inhibition of lipoxygenease, which prevents AA metabolism, protect cells from the toxicity of GSH depletion. (2) We confirmed the AA release is increased during GSH depletion. (3) We showed that exogenous AA is toxic to GSH depleted cells. (5) We demonstrated that products of AA metabolism cause damage to cells, when depleted of GSH. The toxicity of AA is also prevented by inhibition of lipoxygenase, further supporting a role of AA in GSH depletion induced cell death. In summary, our studies provide evidence that depletion of GSH can increase the release and metabolism of AA and that toxic oxygen free radicals produced during AA metabolism, and in particular superoxide, are responsible for GSH depletion induced cell death. A characteristic of Parkinson's disease is GSH depletion in the brain. Our study provides information on the events that lead to toxicity and could help in the design of therapeutic intervention in Parkinson's disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA397697
Entities
People
- Catherine Mytilineou
Organizations
- Icahn School of Medicine at Mount Sinai