Sources of Reactive Oxygen Species Production in Excitotoxin-Stimulated Cerebellar Granule Cells

• Published in: Biochemical and biophysical research communications 1999-03, Vol.256 (2), p.320-324
• Main Authors: Boldyrev, Alexander A., Carpenter, David O., Huentelman, Matthew J., Peters, Craig M., Johnson, Peter
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Cell Survival - drug effects; Cells, Cultured; Cerebellar Cortex - cytology; Cerebellar Cortex - drug effects; Cerebellar Cortex - metabolism; Cyclooxygenase Inhibitors - pharmacology; Electron Transport - drug effects; Flow Cytometry; Fluoresceins; Indomethacin - pharmacology; Kainic Acid - antagonists & inhibitors; Kainic Acid - pharmacology; Monoamine Oxidase Inhibitors - pharmacology; N-Methylaspartate - antagonists & inhibitors; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - metabolism; Neurotoxins - pharmacology; Nialamide - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Rotenone - pharmacology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0325

Reactive oxygen species (ROS) production in rat cerebellar granule cells in the presence of the excitotoxinsN-methyl-d-aspartate (NMDA) and kainic acid (KA) and by the protein kinase C activator phorbol myristate acetate (PMA) was Ca2+-dependent and resulted in decreased cell viability. Exposure of stimulated cells to rotenone (a respiratory chain inhibitor) did not decrease ROS levels and did not affect short-term cell viability. In cells stimulated by NMDA and KA, exposure to indomethacin (a cyclooxygenase inhibitor) and nialamide (a monoamine oxidase inhibitor) caused a decrease in ROS levels and increased cell viability occurred in NMDA-treated cells. In contrast, PMA-stimulated neurons did not show decreased ROS levels when exposed to indomethacin and nialamide. These studies suggest that there is a multiplicity of routes for Ca2+-dependent ROS production in neurons but that ROS generation by cyclooxygenase and monoamine oxidase is not controlled by protein kinase C.