Homocysteine induces glyceraldehyde-3-phosphate dehydrogenase acetylation and apoptosis in the neuroblastoma cell line Neuro2a.
Homocysteine induces glyceraldehyde-3-phosphate dehydrogenase acetylation and apoptosis in the neuroblastoma cell line Neuro2a.
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同型半胱氨酸诱导神经母细胞瘤细胞系 Neuro2a 中甘油醛-3-磷酸脱氢酶乙酰化和细胞凋亡
DOI：
10.1590/1414-431x20154543
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Fang M;Jin A;Zhao Y;Liu X
高血浆同型半胱氨酸（Hcy）水平促进神经退行性疾病的进展。然而，Hcy介导神经毒性的机制尚未阐明。我们观察到，经Hcy孵育后，神经母细胞瘤细胞系Neuro2a的活力呈剂量依赖性下降，并在48小时内诱导细胞凋亡。Hcy的中位有效浓度（EC50）约为5 mM。甘油醛-3-磷酸脱氢酶（GAPDH）核易位和酰化参与了细胞凋亡的调控。我们发现，在5 mM Hcy的存在下，GAPDH的核易位和乙酰化增加，并且在Neuro2a细胞中检测到更高水平的乙酰转移酶p300/CBP。这些发现提示GAPDH参与了Hcy诱导神经元凋亡的机制。这项研究强调了神经退行性疾病的潜在重要途径，以及神经保护治疗的新靶点途径。
High plasma levels of homocysteine (Hcy) promote the progression of neurodegenerative diseases. However, the mechanism by which Hcy mediates neurotoxicity has not been elucidated. We observed that upon incubation with Hcy, the viability of a neuroblastoma cell line Neuro2a declined in a dose-dependent manner, and apoptosis was induced within 48 h. The median effective concentration (EC50) of Hcy was approximately 5 mM. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear translocation and acylation has been implicated in the regulation of apoptosis. We found that nuclear translocation and acetylation of GAPDH increased in the presence of 5 mM Hcy and that higher levels of acetyltransferase p300/CBP were detected in Neuro2a cells. These findings implicate the involvement of GAPDH in the mechanism whereby Hcy induces apoptosis in neurons. This study highlights a potentially important pathway in neurodegenerative disorders, and a novel target pathway for neuroprotective therapy.