Berberine attenuates axonal transport impairment and axonopathy induced by Calyculin A in N2a cells.

Berberine attenuates axonal transport impairment and axonopathy induced by Calyculin A in N2a cells.
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小檗碱减轻 N2a 细胞中 Calyculin A 诱导的轴突运输损伤和轴突病

DOI:
10.1371/journal.pone.0093974
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Chen J
Chen J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu X;Zhou J;Abid MD;Yan H;Huang H;Wan L;Feng Z;Chen J

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黄连是几个世纪以来在传统中药中使用的最有功能的黄连提取物的主要成分。最近的报道表明,黄连素具有预防和治疗阿尔茨海默病(AD)的潜力。以往的研究报道,花盏花素A(CA)损害神经母细胞瘤-2a(N2a)细胞的轴突运输。黄连素可减轻CA诱导的tau过度磷酸化和细胞毒作用。本研究旨在探讨黄连素对CA诱导的N2a细胞轴突运输损伤的影响。结果表明,黄连素对CA诱导的细胞代谢和活性毒性以及tau和神经细丝的过度磷酸化均有保护作用。此外,黄连素还能显著逆转CA所致的轴突运输损伤。黄连素还部分逆转了PP-2A催化亚单位酪氨酸307的磷酸化,并降低了CA诱导的丙二醛水平和超氧化物歧化酶活性(氧化应激标志)。本工作首次证明了黄连素可能通过调节PP-2A的活性和氧化应激而发挥保护CA诱导的轴突运输损伤的作用。我们的研究结果还表明,黄连素可能是治疗阿尔茨海默病的一种潜在药物。
Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD.
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