Abstract
Abstract: Chromogranin A is up‐regulated in the senile plaques of Alzheimer's brain and is a novel activator of microglia, transforming them to a neurotoxic phenotype. Treatment of primary cultures of rat brain microglia or the murine N9 microglial cell line with chromogranin A resulted in nitric oxide production, which triggered microglial apoptosis. Exposure of microglia to chromogranin A resulted in a fall in mitochondrial membrane potential. Mitochondrial depolarisation and apoptosis were reduced significantly by cyclosporin A, but not by the calcineurin inhibitor FK506. Cytochrome c did not translocate from the mitochondria to the cytosol, but its expression became significantly enhanced within the mitochondria. Inhibition of caspase 1 attenuated chromogranin A‐induced microglial apoptosis, but did not prevent mitochondrial depolarisation, indicating that apoptosis occurred downstream of mitochondrial depolarisation. Conversely, staurosporine‐induced microglial apoptosis led to mitochondrial cytochrome c release, but not caspase 1 activation. Our findings provide insight into the pathways controlling activation‐triggered microglial apoptosis and may point to routes for the modulation of microglial evoked neurotoxicity.
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Dates
Type | When |
---|---|
Created | 22 years, 5 months ago (March 12, 2003, 1:44 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 29, 2023, 6:02 a.m.) |
Indexed | 3 months, 3 weeks ago (May 5, 2025, 10:30 a.m.) |
Issued | 25 years, 4 months ago (April 1, 2000) |
Published | 25 years, 4 months ago (April 1, 2000) |
Published Online | 23 years, 7 months ago (Jan. 18, 2002) |
Published Print | 25 years, 4 months ago (April 1, 2000) |
@article{Kingham_2000, title={Microglial Apoptosis Induced by Chromogranin A Is Mediated by Mitochondrial Depolarisation and the Permeability Transition but Not by Cytochrome c Release}, volume={74}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2000.0741452.x}, DOI={10.1046/j.1471-4159.2000.0741452.x}, number={4}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Kingham, Paul J. and Pocock, Jennifer M.}, year={2000}, month=apr, pages={1452–1462} }