Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Sci Rep. 2017 Feb 7;7:41574. doi: 10.1038/srep41574.
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.
广东住血线虫，即鼠肺线虫，是人类嗜酸性脑膜炎和脑膜脑炎的重要病因。将星形胶质细胞与广东住血线虫可溶性抗原共培养可激活 Sonic hedgehog (Shh)信号通路，并通过激活 Bcl-2 抑制星形胶质细胞凋亡。本研究旨在确定广东住血线虫五期幼虫分泌的排泄分泌产物 (ESP) 处理后星形胶质细胞中 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明显下降，但 Shh 信号通路相关蛋白 (Shh、Ptch-1 和 Gli-1) 的表达明显增加。然而，Shh 信号通路激活后星形胶质细胞凋亡明显减少。此外，由于抗氧化剂过氧化氢酶和超氧化物歧化酶水平升高，Shh 通路信号激活后星形胶质细胞中超氧自由基和氢过氧自由基水平明显降低。这些发现表明，广东住血线虫感染小鼠星形胶质细胞中 Shh 信号通路的抗细胞凋亡作用是由于抗氧化剂激活导致氧化应激水平降低所致。
