1. Novel mechanism of increased Ca2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors.
- Author
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Kaja S, Duncan RS, Longoria S, Hilgenberg JD, Payne AJ, Desai NM, Parikh RA, Burroughs SL, Gregg EV, Goad DL, and Koulen P
- Subjects
- Animals, Calcium physiology, Calcium Signaling drug effects, Cell Line, Inositol 1,4,5-Trisphosphate Receptors biosynthesis, Inositol 1,4,5-Trisphosphate Receptors genetics, Intracellular Fluid drug effects, Intracellular Fluid metabolism, Intracellular Space drug effects, Intracellular Space physiology, Mice, Models, Neurological, Nerve Degeneration etiology, Nerve Degeneration physiopathology, Neurons drug effects, Oxidative Stress drug effects, Up-Regulation drug effects, tert-Butylhydroperoxide toxicity, Calcium metabolism, Calcium Signaling physiology, Inositol 1,4,5-Trisphosphate Receptors physiology, Nerve Degeneration metabolism, Neurons metabolism, Oxidative Stress physiology, Up-Regulation physiology
- Abstract
Dysregulation of Ca(2+) signaling following oxidative stress is an important pathophysiological mechanism of many chronic neurodegenerative disorders, including Alzheimer's disease, age-related macular degeneration, glaucomatous and diabetic retinopathies. However, the underlying mechanisms of disturbed intracellular Ca(2+) signaling remain largely unknown. We here describe a novel mechanism for increased intracellular Ca(2+) release following oxidative stress in a neuronal cell line. Using an experimental approach that included quantitative polymerase chain reaction, quantitative immunoblotting, microfluorimetry and the optical imaging of intracellular Ca(2+) release, we show that sub-lethal tert-butyl hydroperoxide-mediated oxidative stress result in a selective up-regulation of type-2 inositol-1,4,5,-trisphophate receptors. This oxidative stress mediated change was detected both at the transcriptional and translational level and functionally resulted in increased Ca(2+) release into the nucleoplasm from the membranes of the nuclear envelope at a given receptor-specific stimulus. Our data describe a novel source of Ca(2+) dysregulation induced by oxidative stress with potential relevance for differential subcellular Ca(2+) signaling specifically within the nucleus and the development of novel neuroprotective strategies in neurodegenerative disorders., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2011
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