title: Activation of Sonic Hedgehog Leads to Survival Enhancement of Astrocytes via the GRP78-Dependent Pathway in Mice Infected with Angiostrongylus cantonensis.
abstract: Angiostrongylus cantonensis infection may cause elevation of ROS and antioxidants in the CSF of infected mice. Astrocytes may protect the surrounding neurons from oxidative stress-induced cell death by secreting Sonic hedgehog (Shh) via the PI3-K/AKT/Bcl-2 pathway. This study was conducted to determine the role of the Shh signaling pathway in A. cantonensis-infected BABL/c mice by coculturing astrocytes with living fifth-stage larvae or soluble antigens. The Shh pathway was activated with corresponding increases in the level of the Shh. Glial fibrillary acidic protein (GFAP) and Shh were increased in astrocyte cocultured with living fifth-stage larvae or soluble antigens. The survival of astrocytes pretreated with Shh was significantly elevated in cocultures with the antigens but reduced by its inhibitor cyclopamine. The expression of GRP78 and Bcl-2 was significantly higher in astrocytes pretreated with recombinant Shh. These findings suggest that the expression of Shh may inhibit cell death by activating Bcl-2 through a GRP78-dependent pathway.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Kuang-Yao
authors.initials: KY
authors.lastname: Chen
authors.affiliation: Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Chien-Ju
authors.initials: CJ
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan ; Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan ; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Lian-Chen
authors.initials: LC
authors.lastname: Wang
mesh_terms: D017185:Angiostrongylus cantonensis / Q000472:pathogenicity; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D053823:Hedgehog Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D005904:Glial Fibrillary Acidic Protein; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D053823:Hedgehog Proteins; C000717248:Hspa5 protein, mouse; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C465570:Shh protein, mouse; C528900:glial fibrillary astrocytic protein, mouse