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Tumor necrosis factor‐α‐induced cell death in U373 cells overexpressing α‐synuclein
Author(s) -
Stefanova Nadia,
Schanda Kathrin,
Klimaschewski Lars,
Poewe Werner,
Wenning Gregor K.,
Reindl Markus
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10662
Subject(s) - alpha synuclein , tumor necrosis factor alpha , biology , programmed cell death , proinflammatory cytokine , neurodegeneration , microbiology and biotechnology , apoptosis , microglia , cancer research , immunology , inflammation , pathology , parkinson's disease , medicine , genetics , disease
Intracellular α‐synuclein inclusion formation in glial cells is frequently seen in Parkinson's disease and multiple system atrophy. Microglial activation in these neurodegenerative disorders suggests that neuroinflammatory responses might interact with α‐synuclein and contribute to the pathogenesis of these disorders. To study the role of tumor necrosis factor‐α (TNF‐α), an important proinflammatory cytokine produced by microglia, on cells overexpressing α‐synuclein we have used the astrocytoma cell line U373 engineered to express C‐terminally truncated α‐synuclein as a fusion protein with red or green fluorescent proteins. We demonstrate that α‐synuclein overexpression augmented TNF‐α‐induced apoptotic cell death in U373 cells by induction of caspase activation. Furthermore, TNF‐α exposure was associated with significant cytoskeletal changes characterized by altered inclusion composition with loss of cytoskeletal proteins and elevation of high‐molecular‐weight α‐synuclein species. We conclude that α‐synuclein overexpression significantly increases the vulnerability of U373 cells to apoptosis through TNF‐α‐mediated pathways. © 2003 Wiley‐Liss, Inc.