S100β induces apoptotic cell death in cultured astrocytes via a nitric oxide-dependent pathway

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Abstract

S100β is a calcium binding protein expressed primarily by astrocytes in the brain. In initiating studies of the toxic signalling pathways activated by high concentrations of S100β, we previously demonstrated that treatment of astrocytes with μM S100β results in a potent stimulation of the mRNA level and enzyme activity of inducible nitric oxide (NO) synthase, an enzyme previously implicated in glial pathology. We provide evidence here that NO formation stimulated by S100β can lead to cell death in astrocytes, with characteristics defined for apoptosis. Incubation of astrocytes with S100β for 48 h results in an increased percentage of astrocytes undergoing apoptotic cell death, as determined with the TUNEL technique, assays of DNA fragmentation and lactate dehydrogenase release. The cell death induced in response to S100β addition correlates with the levels of NO formation, and an inhibitor of nitric oxide synthase attenuates the NO formation elicited by S100β, as well as the cell death. Therefore, we propose that S100β has the potential to be trophic or toxic. Although S100β may be involved in development, homeostasis and repair, chronic overexpression of the protein may mediate toxic responses or even cell death.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1313
Issue number3
DOIs
StatePublished - Oct 11 1996

Bibliographical note

Funding Information:
These studies were supported in part by NIH grants AG11138 and AG10208. We thank Dr. Edith Turkington for providing astrocyte cultures.

Keywords

  • Apoptosis
  • Astrocyte
  • Cytotoxicity
  • Nitric oxide
  • Programmed cell death
  • S100β

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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