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首页> 外文期刊>The European Journal of Neuroscience >Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons.
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Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons.

机译：碳酸钠/碳酸氢盐共转运蛋白NBCn1 / slc4a7增加海马神经元原代培养物中镁耗竭的细胞毒性。

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摘要

Growing evidence suggests that pharmacological inhibition of Na/H exchange and Na/HCO(3) transport provides protection against damage or injury in cardiac ischemia. In this study, we examined the contribution of the sodium/bicarbonate cotransporter NBCn1 (slc4a7) to cytotoxicity in cultured hippocampal neurons of rats. In neurons exposed to extracellular pH (pH(o)) ranging from 6.2 to 8.3, NBCn1 protein expression increased by fivefold at pH < 6.5 compared to the expression at pH(o) 7.4. At pH(o) 6.5, the intracellular pH of neurons was approximately 1 unit lower than that at pH 7.4. Immunochemistry showed a marked increase in NBCn1 immunofluorescence in plasma membranes and cytosol of the soma as well as in dendrites, at pH(o) 6.5. NBCn1 expression also increased by 40% in a prolonged Mg(2+)-free incubation at normal pH(o). Knockdown of NBCn1 in neurons had negligible effect on cell viability. The effect of NBCn1 knockdown on cytotoxicity was then determined by exposing neurons to 0.5 mm glutamate for10 min and measuring lactate dehydrogenase (LDH) release from neurons. Compared to normal incubation (pH(o) 7.2 for 6 h) after glutamate exposure, acidic incubation (pH(o) 6.3 for 6 h) reduced cytotoxicity by 75% for control neurons and 78% for NBCn1-knockdown neurons. Thus, both controls and knockdown neurons showed acidic protection from cytotoxicity. However, in Mg(2+)-free incubation after glutamate exposure, NBCn1 knockdown progressively attenuated cytotoxicity. This attenuation was unaffected by acidic preincubation before glutamate exposure. We conclude that NBCn1 has a dynamic upregulation in low pH(o) and Mg(2+) depletion. NBCn1 is not required for acidic protection, but increases cytotoxicity in Mg(2+)-free conditions.
机译：越来越多的证据表明，Na / H交换和Na / HCO（3）转运的药理学抑制作用可防止心脏缺血中的损伤或损伤。在这项研究中，我们检查了钠/碳酸氢盐共转运蛋白NBCn1（slc4a7）对大鼠海马神经元细胞毒性的影响。在暴露于6.2至8.3的细胞外pH（pH（o））的神经元中，与pH（o）7.4相比，NBCn1蛋白的表达在pH <6.5时增加了五倍。在pH（o）6.5时，神经元的细胞内pH值比在pH 7.4时低约1个单位。免疫化学显示，在pH（o）6.5时，人体质膜和细胞质以及树突中的NBCn1免疫荧光显着增加。 NBCn1表达在正常pH（o）下延长Mg（2+）的孵育中也增加了40％。敲除神经元中的NBCn1对细胞活力的影响可以忽略不计。然后通过将神经元暴露于0.5 mm谷氨酸中10分钟并测量神经元释放的乳酸脱氢酶（LDH）来确定NBCn1敲低对细胞毒性的影响。与谷氨酸暴露后的正常孵育（pH（o）7.2持续6 h）相比，酸性孵育（pH（o）6.3持续6 h）对对照神经元和NBCn1-nockdown神经元的细胞毒性降低了75％。因此，对照和击倒神经元均显示出对细胞毒性的酸性保护。但是，在无Mg（2+）的谷氨酸暴露后孵育中，NBCn1敲低逐渐减弱了细胞毒性。在暴露谷氨酸之前，这种衰减不受酸性预培养的影响。我们得出的结论是，NBCn1在低pH（o）和Mg（2+）耗尽时具有动态上调。 NBCn1不需要进行酸性保护，但是会在无Mg（2+）的条件下增加细胞毒性。

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