Anti-apoptotic effects of Sonic hedgehog signalling through oxidative stress reduction in astrocytes co-cultured with excretory-secretory products of larval Angiostrongylus cantonensis.
Anti-apoptotic effects of Sonic hedgehog signalling through oxidative stress reduction in astrocytes co-cultured with excretory-secretory products of larval Angiostrongylus cantonensis.
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DOI：
10.1038/srep41574
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发表时间：
2017-02-07
影响因子：
4.6
通讯作者：
Wang LC
中科院分区：
文献类型：
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作者：
Chen KY;Chiu CH;Wang LC
广州管圆线虫（鼠肺线虫）是人类嗜酸性脑膜炎和脑膜脑炎的重要病原体。星形胶质细胞与广州星形胶质细胞可溶性抗原共培养可激活Sonic Hedgehog (Shh)信号通路，并通过Bcl-2的激活抑制星形胶质细胞的凋亡。本研究的目的是确定用广州细线虫第五阶段幼虫的排泄分泌产物 (ESP) 处理后，星形胶质细胞中的 Shh 信号通路、细胞凋亡和氧化应激的作用。尽管ESP处理后星形胶质细胞活力显着降低，但Shh信号通路相关蛋白（Shh、Ptch-1和Gli-1）的表达显着增加。然而，激活Shh信号通路后，星形胶质细胞的凋亡显着减少。此外，由于抗氧化剂过氧化氢酶和超氧化物歧化酶水平的增加，星形胶质细胞中的超氧化物和超氧化氢水平在Shh通路信号激活后显着降低。这些发现表明，感染广州曲霉的小鼠星形胶质细胞中Shh信号通路的抗凋亡作用是由于抗氧化剂激活引起的氧化应激水平降低。
Angiostrongylus cantonensis, the rat lungworm, is an important aetiologic agent of eosinophilic meningitis and meningoencephalitis in humans. Co-culturing astrocytes with soluble antigens of A. cantonensis activated the Sonic hedgehog (Shh) signalling pathway and inhibited the apoptosis of astrocytes via the activation of Bcl-2. This study was conducted to determine the roles of the Shh signalling pathway, apoptosis, and oxidative stress in astrocytes after treatment with excretory-secretory products (ESP) from A. cantonensis fifth-stage larvae. Although astrocyte viability was significantly decreased after ESP treatment, the expression of Shh signalling pathway related proteins (Shh, Ptch-1 and Gli-1) was significantly increased. However, apoptosis in astrocytes was significantly decreased after activation of the Shh signalling pathway. Moreover, superoxide and hydrogen superoxide levels in astrocytes were significantly reduced after the activation of Shh pathway signalling due to increasing levels of the antioxidants catalase and superoxide dismutase. These findings indicate that the anti-apoptotic effects of the Shh signalling pathway in the astrocytes of mice infected with A. cantonensis are due to reduced levels of oxidative stress caused by the activation of antioxidants.