Myelin basic protein induces neuron-specific toxicity by directly damaging the neuronal plasma membrane.
Myelin basic protein induces neuron-specific toxicity by directly damaging the neuronal plasma membrane.
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髓磷脂碱性蛋白通过直接损伤神经元质膜诱导神经元特异性毒性
DOI：
10.1371/journal.pone.0108646
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Zhang J;Sun X;Zheng S;Liu X;Jin J;Ren Y;Luo J
中枢神经系统(CNS)损伤可能导致大量脱髓鞘，并导致髓鞘相关蛋白的释放，包括其主要成分髓鞘碱性蛋白(MBP)。据报道，MBP可诱导神经胶质细胞激活，但其对神经元的影响仍鲜为人知。在此，我们发现MBP特异性地结合在神经元质膜的细胞外表面，并在体外诱导神经毒性。MBP对神经元的这种作用是碱性依赖的，因为这种结合被酸性脂类阻止，并被其他碱性蛋白竞争。进一步的研究表明，MBP通过去极化静息膜电位，增加对阳离子和其他分子的通透性，降低膜流动性，导致神经细胞膜的完整性和功能受损。最后，人工脂质体囊泡实验表明，MBP直接干扰了膜的酸性脂双层，导致膜通透性增加。这些结果表明，MBP通过与神经细胞膜表面酸性成分的直接相互作用而产生神经毒性，提示MBP可能参与了中枢神经系统髓鞘损伤的发病机制。
The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.
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影响因子：
2.9
作者：
Boggs, JM;Rangaraj, G;Heng, YM
通讯作者：
Heng, YM
影响因子：
5.5
作者：
Bruckheimer, EM;Schroit, AJ
通讯作者：
Schroit, AJ
影响因子：
2.9
作者：
BOGGS, JM;MOSCARELLO, MA;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
影响因子：
3.3
作者：
Calderon, Tina M.;Eugenin, Eliseo A.;Berman, Joan W.
通讯作者：
Berman, Joan W.
影响因子：
6.1
作者：
CARLTON, WILLIAM W.
通讯作者：
CARLTON, WILLIAM W.