S100beta induces neuronal cell death through nitric oxide release from astrocytes.

Abstract:

:The glial-derived neurotrophic protein S100beta has been implicated in the development and maintenance of the nervous system. S100beta has also been postulated to play a role in mechanisms of neuropathology because of its specific localization and selective overexpression in Alzheimer's disease. However, the exact relationship between S100beta overexpression and neurodegeneration is unclear. Recent data have demonstrated that treatment of cultured rat astrocytes with high concentrations of S100beta results in a potent activation of inducible nitric oxide synthase (iNOS) and a subsequent generation of nitric oxide (NO), which can lead to astrocytic cell death. To investigate whether S100beta-induced NO release from astroctyes might influence neurons, we studied S100beta effects on neuroblastoma B104 cells or primary hippocampal neurons co-cultured with astrocytes. We found that S100beta treatment of astrocyte-neuron co-cultures resulted in neuronal cell death by both necrosis and apoptosis. Neuronal cell death induced by S100beta required the presence of astrocytes and depended on activation of iNOS. Cell death correlated with the levels of NO and was blocked by a specific NOS inhibitor. Our data support the idea that overexpression of S100beta may be an exacerbating factor in the neurodegeneration of Alzheimer's disease.

journal_name

J Neurochem

authors

Hu J,Ferreira A,Van Eldik LJ

doi

10.1046/j.1471-4159.1997.69062294.x

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

2294-301

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

69

pub_type

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