Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
复制标题
铅中毒扰乱少突胶质细胞分化，导致 NCX3 表达降低，诱导细胞内钙超载
DOI：
10.3390/ijms160819096
复制
发表时间：
2015-08-13
影响因子：
5.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Ma T;Wu X;Cai Q;Wang Y;Xiao L;Tian Y;Li H
铅中毒一直是一个严重的健康问题，因为它会永久性地损害中枢神经系统。铅在人体内的慢性蓄积干扰了少突胶质细胞的分化，导致髓鞘功能障碍，但其分子机制尚不清楚。在本研究中，1μM的铅通过下调Olig2、CNPase蛋白的表达来抑制OPC的分化。此外，铅处理还抑制了钠钙交换蛋白3(NCX3)的表达，NCX3是OPC分化过程中钙离子排出质膜的主要方式之一。加入NCX3抑制剂KB-R7943模拟铅中毒后，髓鞘碱性蛋白(MBP)表达减少，细胞分支减少。加铅和KB-R7943处理的细胞内钙离子响应轨迹在恢复时间内没有下降，导致细胞内钙离子浓度升高，降低了MBP的表达。与之相反，NCX3在铅暴露的OPC中高表达，阳性区域的MBP荧光信号和CNPase表达显著增加，恢复了OPC的分化，从而抵消了铅的毒性。综上所述，铅暴露通过诱导细胞内钙超载而影响NCX3的功能，从而干扰OLs的分化。
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca2+) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca2+ response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca2+ concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.