Vitamin K Has the Potential To Protect Neurons From Methylmercury-Induced Cell Death In Vitro
Vitamin K Has the Potential To Protect Neurons From Methylmercury-Induced Cell Death In Vitro
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DOI：
10.1002/jnr.22630
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发表时间：
2011-07-01
影响因子：
4.2
通讯作者：
Yamamoto, Masako
中科院分区：
文献类型：
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作者：
Sakaue, Motoharu;Mori, Naoko;Yamamoto, Masako
维生素K（VK）对神经细胞有保护作用。甲基汞是一种神经毒物，在体内和体外可直接诱导神经元死亡。因此，在本研究中，我们假设VK抑制甲基汞的神经毒性。为了证明我们的假设在体外，我们研究了VKs（叶绿醌，维生素K（1）;甲基萘醌-4，维生素K（2））对甲基汞诱导的大鼠小脑原代培养神经元死亡的保护作用。正如预期的那样，VKs抑制原代培养神经元的死亡。据报道，甲基汞毒性的机制涉及细胞内谷胱甘肽（GSH）的减少。实际上，在本研究中，GSH和GSH诱导剂N-乙酰半胱氨酸的治疗抑制了甲基汞诱导的神经元死亡。因此，我们调查是否VKs也有保护作用，对GSH耗竭诱导的细胞死亡，采用两种GSH还原剂，L-丁硫基亚砜亚胺（BSO）和马来酸二乙酯（DEM），在原代培养的神经元和人神经母细胞瘤IMR-32细胞。VKs治疗影响BSO和DEM诱导的细胞死亡在两种文化。另一方面，细胞内GSH测定表明，VK（2），甲基萘醌-4，不能恢复甲基汞或BSO处理引起的GSH含量减少。这些结果表明，VKs有可能保护神经元免受甲基汞和消耗GSH的试剂的细胞毒性，而不增加细胞内GSH水平。VKs的保护作用可能会导致涉及GSH耗竭的神经疾病治疗的发展。(C)2011 Wiley-Liss，Inc.
Vitamin K (VK) has a protective effect on neural cells. Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro. Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury. To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1); menaquinone-4, vitamin K(2)) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups. As expected, VKs inhibited the death of the primary cultured neurons. It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH). Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study. Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells. Treatment with VKs affected BSO-and DEM-induced cell death in both cultures. On the other hand, the intracellular GSH assay showed that VK(2), menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments. These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels. The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion. (C) 2011 Wiley-Liss, Inc.