Involvement of TNF-alpha in glutamate-induced apoptosis in a differentiated neuronal cell line.

Abstract:

:We examined the involvement of tumor necrosis factor (TNF)-alpha on glutamate-induced cytotoxicity in a differentiated neuronal cell line. In this study, we used nerve growth factor (NGF)-differentiated PC12h cells. Glutamate cytotoxicity was assessed using the MTS and TUNEL assays. To detect TNF-alpha levels in culture supernatants after glutamate exposure, we used ELISA methods. The involvement of caspase-8, which is downstream from TNF receptor 1 (TNF-R1) in glutamate-induced cytotoxicity, was determined by Western blot analysis. The MTS assay showed that the addition of glutamate resulted in dose-dependent cell death, while the TUNEL assay showed that glutamate induced apoptosis in differentiated PC12h cells in a dose-dependent manner. TNF-alpha levels in the supernatant of glutamate-exposed cells were significantly increased compared with those in unexposed cells. In addition, glutamate caused increases in the levels of caspase-8 protein. The increases in caspase-8 levels were ameliorated by pretreatment with soluble TNF-R1. Moreover, soluble TNF-R1 significantly ameliorated the cell death induced by glutamate. These results suggest that TNF-alpha released from neuronal cells may be associated with glutamate-induced neuronal cell death.

journal_name

Brain Res

journal_title

Brain research

authors

Kogo J,Takeba Y,Kumai T,Kitaoka Y,Matsumoto N,Ueno S,Kobayashi S

doi

10.1016/j.brainres.2006.09.006

subject

Has Abstract

pub_date

2006-11-29 00:00:00

pages

201-8

issue

1

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(06)02672-2

journal_volume

1122

pub_type

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