Chromogranin a induces a neurotoxic phenotype in brain microglial cells

Jaroslava Ciesielski-Treska, Gabrielle Ulrich, Laurent Taupenot, Sylvette Chasserot-Golaz, Angelo Corti, Dominique Aunis, Marie France Bader

Research output: Contribution to journalArticle

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Abstract

Chromogranin A (CGA) belongs to a multifunctional protein family widely distributed in secretory vesicles in neurons and neuroendocrine cells. Within the brain, CGA is localized in neurodegenerative areas associated with reactive microglia. By using cultured rodent microglia, we recently described that CGA induces an activated phenotype and the generation of nitric oxide. These findings led us to examine whether CGA might affect neuronal survival, expression of neurofilaments, and high affinity γ-aminobutyric acid uptake in neurons cultured in the presence or absence of microglial cells. We found that CGA was unable to exert a direct toxic effect on neurons but provoked neuronal injury and degeneration in the presence of microglial cells. These effects were observed with natural and recombinant CGA and with a recombinant N-terminal fragment corresponding to residues 1-78. CGA stimulated microglial cells to secrete heat-stable diffusible neurotoxic agents. CGA also induced a marked accumulation of nitric oxide and tumor necrosis factor-α by microglia, but we could not establish a direct correlation between the levels of nitric oxide and tumor necrosis factor-α and the neuronal damage. The possibility that CGA represents an endogenous factor that triggers the microglial responses responsible for the pathogenesis of neuronal degeneration is discussed.

Original languageEnglish
Pages (from-to)14339-14346
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number23
DOIs
Publication statusPublished - Jun 5 1998

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Chromogranins
Chromogranin A
Brain
Phenotype
Microglia
Neurons
Nitric Oxide
Tumor Necrosis Factor-alpha
Aminobutyrates
Neuroendocrine Cells
Intermediate Filaments
Poisons
Secretory Vesicles
Rodentia
Hot Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ciesielski-Treska, J., Ulrich, G., Taupenot, L., Chasserot-Golaz, S., Corti, A., Aunis, D., & Bader, M. F. (1998). Chromogranin a induces a neurotoxic phenotype in brain microglial cells. Journal of Biological Chemistry, 273(23), 14339-14346. https://doi.org/10.1074/jbc.273.23.14339

Chromogranin a induces a neurotoxic phenotype in brain microglial cells. / Ciesielski-Treska, Jaroslava; Ulrich, Gabrielle; Taupenot, Laurent; Chasserot-Golaz, Sylvette; Corti, Angelo; Aunis, Dominique; Bader, Marie France.

In: Journal of Biological Chemistry, Vol. 273, No. 23, 05.06.1998, p. 14339-14346.

Research output: Contribution to journalArticle

Ciesielski-Treska, J, Ulrich, G, Taupenot, L, Chasserot-Golaz, S, Corti, A, Aunis, D & Bader, MF 1998, 'Chromogranin a induces a neurotoxic phenotype in brain microglial cells', Journal of Biological Chemistry, vol. 273, no. 23, pp. 14339-14346. https://doi.org/10.1074/jbc.273.23.14339
Ciesielski-Treska J, Ulrich G, Taupenot L, Chasserot-Golaz S, Corti A, Aunis D et al. Chromogranin a induces a neurotoxic phenotype in brain microglial cells. Journal of Biological Chemistry. 1998 Jun 5;273(23):14339-14346. https://doi.org/10.1074/jbc.273.23.14339
Ciesielski-Treska, Jaroslava ; Ulrich, Gabrielle ; Taupenot, Laurent ; Chasserot-Golaz, Sylvette ; Corti, Angelo ; Aunis, Dominique ; Bader, Marie France. / Chromogranin a induces a neurotoxic phenotype in brain microglial cells. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 23. pp. 14339-14346.
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