Activation of Sonic hedgehog pathway plays an important role in the protection of astrocytes from the infection of Angiostrongylus cantonensis
| Autor: | Kuang Yao Chen, 陳光耀 |
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| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Angiostrongylus cantonensis, the rat lungworm, is an important etiologic agent of eosinophilic meningitis or eosinophilic meningoencephalitis in humans. Angiostrongyliasis is also an important zoonosis in Taiwan. Human is a non permissive host for A. cantonesis, after infection of the third-stage larvae, this parasite does not complete developmental cycle. The fifth-stage larvae (L5) remain in brain induce inflammatory reaction and neurological clinical manifestations in patients. Oxidative stress was increased in the cerebrospinal fluid of infected mice with infection. These stress may induce meningitis and injuries in the host brain. In our previous study, immune response and astrocytes activation were found in brain of infected mice. Moreover, the expressions of Sonic hedgehog (Shh) signaling pathway related genes (shh, ptc, smo and gli-1) were increased after A. cantonensis infection in microarray dataset. This study was conducted to determine the protective role of the Shh signaling pathway in astrocytes with A. cantonensis infection. The Shh signaling pathway was activated in astrocytes by treatment with living L5 or soluble antigen of L5, which in turn inhibit cell death by activating Bcl-2 through the GRP78-dependent pathway. Excretory/secretory products (ESP) is important for the interaction between parasitic helminths and their hosts. It is a key factor for the invasion, development, and survival of the parasites. ESP can also regulate immune responses, oxidative stress, and cell survival of the host. Although the cell viability of astrocytes was decreased by treating of L5 ESP, the expressions of Shh signaling pathway related proteins (Shh, Ptch-1, and Gli-1) were increased. After activating Shh signaling pathway in astrocytes, reactive oxygen species (ROS) (superoxide and H2O2) were reduced, the antioxidants (catalase and superoxide dismutase) were increased and cell death and apoptosis were decreased. The results indicate that the activation of Shh signaling pathway can protect astrocytes in living L5, soluble antigen of L5 and ESP treatment. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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