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

Abstract：

:The purpose of this study was to determine the effects of specific proinflammatory cytokines interleukin-6 (Il-6), interleukin-1beta (Il-1beta), interferon-gamma (IFN), and tumor necrosis factor-alpha (TNFalpha), on content and distribution of alpha-synuclein (alpha-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-1beta decreased alpha-synuclein and tau at 18 and 96 h; TNFalpha inversely reduced alpha-synuclein and increased ubiquitin content. Combinations of Il-1beta and IFN produced a robust increase of alpha-synuclein and tau at 2 h. Consecutive low doses of Il-6 produced only minor increases in alpha-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 x 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 alpha-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.

journal_name

Brain Res

journal_title

Brain research

authors

Bick RJ,Poindexter BJ,Kott MM,Liang YA,Dinh K,Kaur B,Bick DL,Doursout MF,Schiess MC

doi

10.1016/j.brainres.2008.03.081

subject

Has Abstract

pub_date

2008-06-27 00:00:00

pages

203-12

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(08)00823-8

journal_volume

1217

pub_type

杂志文章

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