Zinc chelation potentiates excitotoxicity

Q. D. Nguyen, J. E. Heng, E. B. Dreyer

Research output: Contribution to journalArticle

Abstract

Purpose: Zinc is an essential part of cellular metabolism, but its role in the retina has not been fully elucidated. We have established that zinc dictation is directly toxic to retinal ganglion cells in vitro, and that this toxicity is mediated through the NMDA receptor. Furthermore, this toxicity appears to involve a perturbation of the mitochondria's ability to buffer cellular calcium levels. Other investigators have demonstrated that the ability of mitochondria to buffer calcium is critical for the cell to resist an excitotoxic challenge. Methods: Dissociated neonatal rat retinal ganglion cells, previously labeled with the mitochondria! sensitive dye rhodamine-2, were incubated with one of several zinc chelators. Sister cultures were also labeled with the calcium sensitive dye calcium green. Results; Zinc chelation caused an approximate doubling in calcium-dependent rhodamine-2 fluorescence over a period of 3-4 minutes. Zinc chelation did, however, cause a decrease in calcium green fluorescence, suggesting a decline in cytosolic calcium. Both changes could be blocked with either rotenone or FCCP. Conclusions: These results indicate that the toxicity seen with zinc chelation is most likely mediated through a perturbation in mitochondria! calcium homeostasis.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - 1997
Externally publishedYes

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Zinc
Calcium
Mitochondria
Rhodamines
Retinal Ganglion Cells
Buffers
Fluorescence
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Rotenone
Poisons
Chelating Agents
N-Methyl-D-Aspartate Receptors
Retina
Homeostasis
Coloring Agents
Research Personnel
calcium green

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Nguyen, Q. D., Heng, J. E., & Dreyer, E. B. (1997). Zinc chelation potentiates excitotoxicity. Investigative Ophthalmology and Visual Science, 38(4).

Zinc chelation potentiates excitotoxicity. / Nguyen, Q. D.; Heng, J. E.; Dreyer, E. B.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 4, 1997.

Research output: Contribution to journalArticle

Nguyen, QD, Heng, JE & Dreyer, EB 1997, 'Zinc chelation potentiates excitotoxicity', Investigative Ophthalmology and Visual Science, vol. 38, no. 4.
Nguyen, Q. D. ; Heng, J. E. ; Dreyer, E. B. / Zinc chelation potentiates excitotoxicity. In: Investigative Ophthalmology and Visual Science. 1997 ; Vol. 38, No. 4.
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