Summary
Na+/H+ exchanger isoform 1 (NHE1) is a major acid extrusion mechanism following intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to disruption of Na+ homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Oxygen and glucose deprivation (OGD) for 3 hours followed by 21 hours of reoxygenation (REOX) led to 68 ± 10% cell death. Inhibition of NHE1 with the potent inhibitor HOE 642 or genetic ablation of NHE1 reduced OGD-induced cell death by ∼40% to 50% (p < 0:05). In NHE1+/+ neurons, OGD/REOX triggered significant increases in Nai+ and Cai2+. Genetic ablation of NHE1 and HOE 642 treatment reduced the rise of Nai+ by ∼40% to 50% and abolished the OGD/REOX-mediated Ca2+ accumulation. Moreover, mitochondrial cytochrome C release was significantly attenuated by inhibition of NHE1 activity. These results imply that NHE1 activity disrupts Na+ and Ca2+ homeostasis and contributes to ischemic neuronal damage.
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Luo, J., Chen, H., Kintner, D.B., Shull, G.E., Sun, D. (2006). Inhibition of Na+/H+ exchanger isoform 1 attenuates mitochondrial cytochrome C release in cortical neurons following in vitro ischemia. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_52
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DOI: https://doi.org/10.1007/3-211-30714-1_52
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