Novel mechanism of increased Ca 2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors

S. Kaja, R. S. Duncan, S. Longoria, J. D. Hilgenberg, A. J. Payne, N. M. Desai, R. A. Parikh, S. L. Burroughs, E. V. Gregg, D. L. Goad, P. Koulen

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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.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalNeuroscience
Volume175
DOIs
StatePublished - Feb 17 2011

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Kaja, S., Duncan, R. S., Longoria, S., Hilgenberg, J. D., Payne, A. J., Desai, N. M., Parikh, R. A., Burroughs, S. L., Gregg, E. V., Goad, D. L., & Koulen, P. (2011). Novel mechanism of increased Ca 2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors. Neuroscience, 175, 281-291. https://doi.org/10.1016/j.neuroscience.2010.11.010