The heme precursor delta-aminolevulinate blocks peripheral myelin formation.
The heme precursor delta-aminolevulinate blocks peripheral myelin formation.
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DOI：
10.1111/j.1471-4159.2008.05552.x
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发表时间：
2008-09
影响因子：
4.7
通讯作者：
Notterpek L
中科院分区：
文献类型：
--
作者：
Felitsyn N;McLeod C;Shroads AL;Stacpoole PW;Notterpek L
δ-氨基乙酰丙酸（δ-ALA）是一种血红素前体，与卟啉症和酪氨酸血症I型相关的神经系统并发症有关。在接受研究药物二氯醋酸盐（DCA）治疗的动物和患者的尿液中，Δ-ALA也升高。我们推测δ-ALA可能是在接受DCA的受试者中观察到的周围神经病变的部分原因。为了验证这一假设，将雪旺细胞和感觉神经元的髓鞘形成共培养物暴露于δ-ALA（0.1-1 mM），并分析神经蛋白和脂质以及氧化应激标志物的表达。髓鞘形成样品暴露于δ-ALA与髓鞘相关脂质和蛋白质（包括髓鞘蛋白零和外周髓鞘蛋白22）水平的显著降低相关。我们还观察到用δ-ALA处理后，蛋白质羰基化和羟基壬烯醛和丙二醛的形成增加。孤立的雪旺细胞和神经元的研究表明，神经胶质细胞比神经元更容易受到这种促氧化剂的影响，这是基于神经胶质细胞中线粒体呼吸链蛋白表达的选择性降低，而不是神经元细胞。这些结果表明，δ-ALA的神经病变作用至少部分归因于其促氧化特性，其损伤髓鞘形成的雪旺细胞。
Delta-aminolevulinic acid (δ-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that δ-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to δ-ALA (0.1–1 mM) and analyzed for the expression of neural proteins and lipids and markers of oxidative stress. Exposure of myelinating samples to δ-ALA is associated with a pronounced reduction in the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22. We also observed an increase in protein carbonylation and the formation of hydroxynonenal and malondialdehyde after treatment with δ-ALA. Studies of isolated Schwann cells and neurons indicate that glial cells are more vulnerable to this pro-oxidant than neurons, based on a selective decrease in the expression of mitochondrial respiratory chain proteins in glial, but not in neuronal, cells. These results suggest that the neuropathic effects of δ-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells.
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影响因子：
7.4
作者：
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通讯作者：
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