Abstract
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.
Highlights
By activating Bcl-2 and inhibiting Bax through the PI3-K/AKT/Bcl-2 pathway[12]
Apoptosis in astrocytes co-cultured with Excretory-secretory products (ESPs) or bovine serum albumin (BSA) for 4 h was detected by an apoptosis assay
These findings suggest that ESPs induce the apoptosis of astrocytes
Summary
By activating Bcl-2 and inhibiting Bax through the PI3-K/AKT/Bcl-2 pathway[12] These findings indicate an association between the Shh signalling pathway and oxidative stress. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) (H2O2, O2− and OH−) and their subsequent neutralization[15,16]. It is an important pathological feature associated with the neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease[17,18,19]. We prepared and used ESP from L5 A. cantonensis to study the relationship between the Shh pathway, oxidative stress and apoptosis. The anti-apoptotic effects of Shh signalling are attributed to reduced oxidative stress levels
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