Anti-apoptotic effects of Sonic hedgehog signalling through oxidative stress reduction in astrocytes co-cultured with excretory-secretory products of larval Angiostrongylus cantonensis.
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.
Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Kuang-Yao
KY
Chen
Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Cheng-Hsun
CH
Chiu
Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Lian-Chen
LC
Wang
D017185:Angiostrongylus cantonensis / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D018920:Coculture Techniques; D053823:Hedgehog Proteins / Q000378:metabolism*; D006790:Host-Parasite Interactions; D007814:Larva; D051379:Mice; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
D000947:Antigens, Helminth; D053823:Hedgehog Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase