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Deficiency of glia maturation factor suppresses 1‐methyl‐4‐ phenylpyridinium induced toxicity in primary cultures of mouse astrocytes
Author(s) -
Khan Mohammad M,
Javed Hayate,
Zaheer Asgar
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.890.2
Subject(s) - proinflammatory cytokine , astrocyte , nitric oxide , chemokine , reactive oxygen species , microglia , chemistry , toxicity , neuroglia , microbiology and biotechnology , biology , immunology , inflammation , endocrinology , central nervous system , organic chemistry
Glia maturation factor (GMF), a brain specific protein, is isolated, sequenced and cloned in our laboratory, predominantly localized in astrocytes. In the present studies, we demonstrate that deficiency of GMF in astrocytes limits the production of reactive oxygen species (ROS) and suppresses the NF‐kB mediated inflammatory responses in 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced toxicity. Primary astrocytes obtained from wild type (Wt) and GMF‐KO mice were treated with 5, 10 and 20 ìM MPP+ for 24, 48 and 72 hr. Our results show decrease production of ROS and nitric oxide in GMF‐KO astrocytes following MPP+ treatment. In contrast, astrocytes derived from Wt mice exhibited increase level of ROS along with enhance level of nitric oxide. Additionally, we found decrease activity of nuclear factor‐êB, and reduce levels of proinflammatory cytokines/chemokines in GMF‐KO astrocytes compared to Wt astrocytes. The overall data suggests that GMF‐KO astrocytes were more resistant to MPP+ toxicity compare to Wt astrocytes. These findings provide the first evidence that GMF deficiency protects astrocytes from MPP+‐induced toxicity by reducing the ROS production along with diminished levels of NF‐kB and proinflammatory cytokine/chemokine expression. (Supported by VA Merit Review award and NINDS grant NS073670).