CHP调节NHE1活性影响细胞生长和死亡

钠氢离子交换蛋白(NHE)定位于细胞膜,它的重要功能是调节细胞内pH值。钙调磷酸酶B同源蛋白(CHP)是NHE必要的活性调节亚单位。研究了NHE1结合CHP与否对细胞生长和死亡的影响。结果显示,CHP结合于NHE1细胞质调节区域之中靠近细胞膜部位,二者以疏水键结合而形成蛋白IV级结构。在细胞内pH5.4的非生理条件下,表达没有CHP结合能力的突变体NHE1-4R细胞只有表达野生型NHE细胞7.6%的最大摄取钠活性;在细胞内pH7.2的生理条件下,这个比例降至1.2%的摄取钠活性。与野生型NHE1比较,有血清时表达突变体NHE1-4R的细胞生长速度减慢;在血清饥饿时这些细胞因自身的胞浆酸性化而死亡数增加。实验结果证明,CHP是NHE1生理活性的必要调节因子,它能影响细胞生长和死亡。

CHP Regulated NHE1 Activity Affects Cell Growth and Death

The Na /H exchanger (NHE) is an important membrane protein to maintain the intracellular pH (pH_i). Calcineurin B homologous protein (CHP) is an essential regulation cofactor for NHE. CHP binding site is identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchanger. NHE and CHP are combined together by hydrophobic bond. At the condition of pH_i 5.4, the 22Na uptake activity (Vmax) of the cell expressing CHP binding-defective mutation of NHE (mutant NHE1- 4R) is 7.6% of the cell expressing wild type NHE1; however, at physiologic pH_i 7.2, the 22Na uptake activity is only 1.2%. The growth of the cell expressing mutant NHE1- 4R is slower. Under the condition of long serum starvation, death of the cell expressing mutant NHE1- 4R was increased by cytoplasmic self-acidification. The result indicated CHP is an essential regulation factor to support the physiology activity of NHE1.