title: Glia maturation factor deficiency suppresses 1-methyl-4-phenylpyridinium-induced oxidative stress in astrocytes.
abstract: Inflammation is closely intertwined with pathogenesis of Parkinson's disease (PD). Increasing evidence suggests that inhibition of glia-mediated inflammation might represent a promising therapeutic target for PD. Glia maturation factor (GMF), an inflammatory protein, predominantly localized in astrocytes is previously isolated, sequenced and cloned in our laboratory. In the present investigation, we demonstrate that GMF-deficiency in astrocytes upregulates the antioxidant status and limit the extent of lipid peroxidation and production of reactive oxygen species (ROS) along with diminished nuclear factor-κB-mediated inflammatory responses in 1-methyl-4-phenylpyridinium (MPP(+))-induced toxicity. Primary astrocytes obtained from wild-type (Wt) and GMF-deficient (GMF-KO) mice were treated with 5, 10, and 20 μM MPP(+) for 24, 48, and 72 h in vitro. Our results show decreased release of ROS and increased level of glutathione in astrocytes obtained from GMF-KO mice when compared to astrocytes derived from Wt mice following MPP(+) treatment. Additionally, we found decreased activity of NF-κB, and reduced levels of proinflammatory tumor necrosis factor- α, interleukin-1β (IL-1β), IL-17, IL-33, and chemokine (C-C motif) ligand 2 (CCL2) in GMF-KO astrocytes when compared to Wt astrocytes. Our overall results suggest that GMF-KO astrocytes are significantly resistant to MPP(+) toxicity when compared to Wt astrocytes.
authors.affiliation: Department of Neurology, University of Iowa, Iowa City, IA, 52242, USA.
authors.forename: Mohammad Moshahid
authors.initials: MM
authors.lastname: Khan
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.forename: Smita
authors.initials: S
authors.lastname: Zaheer
authors.forename: Asgar
authors.initials: A
authors.lastname: Zaheer
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D020904:Glia Maturation Factor / Q000172:deficiency* / Q000235:genetics; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020904:Glia Maturation Factor; D007378:Interleukins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D015655:1-Methyl-4-phenylpyridinium