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 language | English |
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Pages (from-to) | 239-245 |
Number of pages | 7 |
Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
Volume | 1313 |
Issue number | 3 |
DOIs | |
State | Published - 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.
Funding
These studies were supported in part by NIH grants AG11138 and AG10208. We thank Dr. Edith Turkington for providing astrocyte cultures.
Funders | Funder number |
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National Institutes of Health (NIH) | AG10208 |
National Institute on Aging | R01AG011138 |
Keywords
- Apoptosis
- Astrocyte
- Cytotoxicity
- Nitric oxide
- Programmed cell death
- S100β
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology