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- W2743155227 abstract "P83 Regulation of [Ca 2+ ] i is altered in neurons during ischemic injury in stroke, but the precise mechanism(s) underlying the Ca 2+ dysregulation are not known. The plasma membrane Ca 2+ -ATPase (PMCA) is one of the two main Ca 2+ extrusion systems that play a critical role in maintaining neuronal Ca 2+ homeostasis. We have substantial evidence showing that this enzyme is very sensitive to oxidative stress. When exposed to very low concentrations of physiologically relevant oxidants, the PMCA has been shown to form high molecular weight aggregates and this is accompanied by the decline in its enzymatic activity. Because stroke-induced hypoxia is associated with the overproduction of reactive oxygen species (ROS) and a loss of Ca 2+ homeostasis, we carried out studies to determine if the PMCA is modified in an in vivo animal model of stroke. Global ischemia was induced in Sprague Dawley rats by occlusion of the common carotid arteries for defined time periods. The V max of PMCA activity in brain homogenates as well as in purified synaptic plasma membranes was significantly reduced following occlusion of the vessels, and the reduction was proportional to the time of ischemia. The loss in PMCA activity could not be reversed by addition of exogenous ATP, suggesting an alteration in the protein itself. Immunoblots of the synaptic membranes run under non-reducing conditions showed crosslinking of PMCA molecules to form high molecular weight adducts, and this too increased with increasing periods of ischemia. The PMCA aggregates were partially reversed under reducing conditions, indicating the involvement of sulphydryl group oxidation. These observations support the hypothesis that increased formation of ROS under ischemic conditions can oxidatively modify specific proteins critical for the regulation of free [Ca 2+ ] i levels. Such oxidative damage is likely to contribute to the loss of neuronal Ca 2+ regulation and neuronal viability in stroke. (Supported by AHA 9960343Z, AG 12993, and the Higuchi Biosciences Center, University of Kansas)" @default.
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- W2743155227 date "2001-01-01" @default.
- W2743155227 modified "2023-09-28" @default.
- W2743155227 title "Modification of Synaptic Plasma Membrane Ca2+-ATPase in Ischemic Injury in an Animal Model of Global Ischemia" @default.
- W2743155227 doi "https://doi.org/10.1161/01.str.32.suppl_1.354-a" @default.
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