Cytokines disrupt intracellular patterns of Parkinson's disease-associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells

Roger J. Bick, Brian J. Poindexter, Marylee M. Kott, Yang an Liang, Kha Dinh, Berneet Kaur, Diane L M Bick, Marie Francoise Doursout, Mya C. Schiess

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The purpose of this study was to determine the effects of specific proinflammatory cytokines interleukin-6 (Il-6), interleukin-1β (Il-1β), interferon-gamma (IFN), and tumor necrosis factor-alpha (TNFα), on content and distribution of alpha-synuclein (α-synuclein), tau and ubiquitin in human derived cultured glial cells. Exposure paradigms mimicked acute (2 h), intermediate (18 h) and prolonged time frames (96 h); consisting of single or repeated low doses (10 ng/ml) or high doses (50 ng/ml), consistent with either mild or serious systemic infectious/inflammatory responses. Images of intracellular protein content and distribution were reconstructed from emission patterns generated by fluorescence deconvolution microscopy. Minor alterations were seen in protein content with IFN; Il-1β decreased α-synuclein and tau at 18 and 96 h; TNFα inversely reduced α-synuclein and increased ubiquitin content. Combinations of Il-1β and IFN produced a robust increase of α-synuclein and tau at 2 h. Consecutive low doses of Il-6 produced only minor increases in α-synuclein and ubiquitin after 4 h, whereas a single high dose resulted in major increases for all three proteins over the first 18 h. Protein localization patterns were distinctly different and were altered dependent upon cytokine treatment. A high dose exposure (2 × 50 ng/ml) with Il-6 and IFN demonstrated that protein increases and dispersals could be sustained and that the normal perinuclear tau and peripheral α-synuclein patterns were disrupted. These results support the postulate that specific cytokines affect temporal protein changes with concomitant pattern disruptions, possibly reflecting a mechanism of cell dysfunction in Parkinson's degeneration.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalBrain Research
Volume1217
DOIs
StatePublished - Jun 27 2008
Externally publishedYes

Keywords

  • Fluorescence
  • Glial cell
  • Imaging
  • Microscopy
  • Parkinson's disease
  • Protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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  • Cite this

    Bick, R. J., Poindexter, B. J., Kott, M. M., Liang, Y. A., Dinh, K., Kaur, B., Bick, D. L. M., Doursout, M. F., & Schiess, M. C. (2008). Cytokines disrupt intracellular patterns of Parkinson's disease-associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells. Brain Research, 1217, 203-212. https://doi.org/10.1016/j.brainres.2008.03.081