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Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes

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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.

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Abbreviations

CCL2:

(C–C motif) ligand 2

DA:

Dopamine

ELISA:

Enzyme-linked immunosorbent assay

GMF:

Glia maturation factor

GMF-KO:

GMF knockout

GSH:

Glutathione

HRP:

Horseradish peroxidase

IL-1:

Interleukin-1

iNOS:

Inducible nitric oxide synthase

LDH:

Lactate dehydrogenase

MPP:

1-Methyl-4-phenyl-pyridine

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

NF-kB:

Nuclear transcription factor-κB

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SDS:

Sodium dodecyl sulfate

TBARS:

Thiobarbituric acid reactive substance

TNF-α:

Tumor necrosis factor-alpha

Wt:

Wild-type

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Acknowledgments

This work was supported by the Department of Veterans Affairs Merit Review award (to AZ) and by the National Institute of Neurological Disorders and Stroke grants NS073670 (to AZ).

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Authors and Affiliations

  1. Department of Neurology, University of Iowa, Iowa City, IA, 52242, USA

    Mohammad Moshahid Khan, Duraisamy Kempuraj, Smita Zaheer & Asgar Zaheer

  2. VA Health Care System, Iowa City, IA, USA

    Asgar Zaheer

  3. Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA

    Asgar Zaheer

Authors
  1. Mohammad Moshahid Khan
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  2. Duraisamy Kempuraj
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  3. Smita Zaheer
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  4. Asgar Zaheer
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Correspondence to Asgar Zaheer.

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Khan, M.M., Kempuraj, D., Zaheer, S. et al. Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes. J Mol Neurosci 53, 590–599 (2014). https://doi.org/10.1007/s12031-013-0225-z

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