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Protective effects of FK506 against glutamate-induced neurotoxicity in retinal cell culture.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 1998 Jun; Vol. 39 (7), pp. 1227-32. - Publication Year :
- 1998
-
Abstract
- Purpose: To examine the effects of FK506 on glutamate neurotoxicity in cultured retinal neurons.<br />Methods: Experiments were performed with primary retinal cultures obtained from 17- to 19-day-old rat fetuses. To assess the effects of FK506 and other drugs on glutamate neurotoxicity, cultures were treated with a drug beginning 10 minutes before application of glutamate and continuing during the subsequent 10 minutes of glutamate exposure. The treated cells were then incubated for 1 hour in a drug-free and glutamate-free medium. After a 1-hour incubation, cell viability was quantitatively measured by the trypan blue exclusion method.<br />Results: Brief exposure to glutamate markedly decreased cell viability. FK506 protected against glutamate neurotoxicity in a dose-dependent manner. Rapamycin is a competitive inhibitor of FK506 that binds FK506 binding protein. Simultaneous application of rapamycin and FK506 negated the protective effects of FK506. Cyclosporin A, which binds and inhibits calcineurin, mimicked the protective effects of FK506. Treatment with FK506 did not affect the intracellular maximum Ca2+ concentration induced by glutamate application. Although FK506 exhibited protective action against Ca2+ ionophore-induced neurotoxicity, it had no effect on nitric oxide-induced neurotoxicity. Treatment with FK506 reduced the activity of nitric oxide synthase (NOS).<br />Conclusion: FK506 protected against glutamate neurotoxicity by inhibiting NOS activity in cultured retinal neurons.
- Subjects :
- Animals
Calcineurin Inhibitors
Calcium metabolism
Cell Culture Techniques
Cell Survival drug effects
Cyclosporine pharmacology
Dose-Response Relationship, Drug
Fetus
Neurons enzymology
Nitric Oxide metabolism
Nitric Oxide Synthase metabolism
Polyenes pharmacology
Rats
Retina enzymology
Sirolimus
Tacrolimus antagonists & inhibitors
Glutamic Acid toxicity
Neurons drug effects
Retina drug effects
Tacrolimus pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0146-0404
- Volume :
- 39
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 9620083