Novel mechanism of increased Ca2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors.

Autor: Kaja S; Department of Ophthalmology and BasicMedical Science, University of Missouri, Kansas City, MO 64108, USA. kajas@umkc.edu, Duncan RS, Longoria S, Hilgenberg JD, Payne AJ, Desai NM, Parikh RA, Burroughs SL, Gregg EV, Goad DL, Koulen P
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2011 Feb 23; Vol. 175, pp. 281-91. Date of Electronic Publication: 2010 Nov 11.
DOI: 10.1016/j.neuroscience.2010.11.010
Abstrakt: 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.)
Databáze: MEDLINE
Externí odkaz: