The electrogenic sodium bicarbonate cotransporter: Developmental expression in rat brain and possible role in acid vulnerability
The electrogenic sodium bicarbonate cotransporter: Developmental expression in rat brain and possible role in acid vulnerability
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DOI：
10.1523/jneurosci.20-03-01001.2000
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发表时间：
2000-02-01
影响因子：
5.3
通讯作者：
Monyer, H
中科院分区：
文献类型：
--
作者：
Giffard, RG;Papadopoulos, MC;Monyer, H
产电碳酸氢钠协同转运蛋白（NBC）在脑胶质细胞中表达，并在细胞内和细胞外pH值的调节中起着重要作用。已经注意到神经元和胶质细胞之间对酸中毒的差异脆弱性，并可能导致脑缺血后的梗死。离子取代研究和4，4 '-二异硫氰基芪-2，2'-二磺酸对损伤的抑制表明，NBC参与了星形胶质细胞对酸性损伤的脆弱性。最近，从肾脏和胰腺中克隆了两个在5 '端非翻译序列和N端编码序列上不同的NBC cDNA。我们从大鼠脑中克隆了这些cDNA之一，并在此证明该克隆在非洲爪蟾卵母细胞中的表达是有功能的。我们通过原位杂交确定了NBC在脑中的发育和区域表达。在胚胎第17天在脊髓中观察到表达，而在脑中的表达在大约出生后第0天（P0）首次观察到，在P15时增加，并且在成人脑中持续存在。表达广泛分布于小脑、皮质、嗅球和皮质下结构。原位杂交信号的细胞分辨率和胶质细胞酸性蛋白的双标记与NBC的胶质细胞定位一致。在正常情况下不表达这种转运蛋白的3 T3细胞中NBC的表达使它们容易受到酸损伤。表达谱表明，这种转运蛋白在大脑发育的后期阶段是至关重要的，可能是导致围产期与成人脑缺血损伤的不同模式的因素之一。
The electrogenic sodium bicarbonate cotransporter (NBC) is expressed in glial cells in the brain and plays an important role in the regulation of both intracellular and extracellular pH. Differential vulnerability to acidosis between neurons and glia has been noted and may contribute to infarction after cerebral ischemia. Ionic substitution studies and inhibition of injury by 4,4'-di-isothiocyanostilbene-2,2'-disulfonic acid suggest that NBC is involved in astrocyte vulnerability to acidic injury. Recently two NBC cDNAs differing in 5'-untranslated and N-terminal coding sequence have been cloned from kidney and pancreas. We cloned one of these cDNAs from rat brain and demonstrate here that the clone is functional by expression in Xenopus oocytes. We determined the developmental and regional expression of NBC in the brain by in situ hybridization. Expression was observed in the spinal cord at embryonic day 17, whereas expression in brain was first seen at approximately postnatal day 0 (P0), increased at P15, and persisted in the adult brain. Expression was widespread throughout the cerebellum, cortex, olfactory bulb, and subcortical structures. Cellular resolution of the in situ hybridization signal and double labeling for glial fibrillary acidic protein were consistent with a glial localization for NBC. Expression of NBC in 3T3 cells that do not normally express this transporter rendered them vulnerable to acid injury. The expression profile suggests that this transporter is critical during the later stages of brain development and could be one of the factors contributing to the different patterns of injury seen in perinatal versus adult cerebral ischemia.