Endoplasmic reticulum Ca2+ dysregulation and endoplasmic reticulum stress following in vitro neuronal ischemia: role of Na+-K+-Cl- cotransporter

摘要: We investigated the role of Na(+)-K(+)-Cl(-) cotransporter (NKCC1) in conjunction with Na(+)/Ca(2+) exchanger (NCX) disruption endoplasmic reticulum (ER) Ca(2+) homeostasis and ER stress development primary cortical neurons following vitro ischemia. Oxygen-glucose deprivation (OGD) reoxygenation (REOX) caused a rise [Na(+)](cyt) which was accompanied by an elevation [Ca(2+)](cyt). Inhibition NKCC1 its potent inhibitor bumetanide abolished OGD/REOX-induced Moreover, OGD significantly increased Ca(2+)(ER) accumulation. Following REOX, biphasic change occurred initial release sensitive to inositol 1,4,5-trisphosphate receptor (IP(3)R) inhibition subsequent refilling stores. activity or genetic ablation prevented Ca(2+)(ER). A similar result obtained reversed mode operation NCX (NCX(rev)). OGD/REOX also triggered transient increase glucose regulated protein 78 (GRP78), phospho-form alpha subunit eukaryotic initiation factor 2 (p-eIF2alpha), cleaved caspase 12 proteins. Pre-treatment inhibited upregulation GRP78 attenuated level p-eIF2alpha. reduced cytochrome C neuronal death. Taken together, these results suggest that NCX(rev) may be involved ischemic cell damage part via disrupting function.