Thrombin receptor peptides induce shape change in neonatal murine astrocytes in culture
✍ Scribed by K. L. Beecher; T. T. Andersen; J. W. Fenton II; B. W. Festoff
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 768 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Astrocytes appear star-shaped in the brain, increasingly so after injury. When astroglia are cultured in serum-containing medium, they exhibit a flat, fibroblast-like morphology. In serum-free medium, astrocytes become stellate, with many long processes. The serine protease a-thrombin mimics the effects of serum at subnanomolar concentrations, whereas the thrombin-inhibiting serpin, protease nexin I (PNI), reverses the thrombin effect. In our current experiments, murine neonatal spinal cord astrocytes became stellate after 4 hr in serum-free medium, while cortical astrocytes required 12 hr in serum-free medium for stellation. Astrocytes from either region flattened after 60 min in medium containing 3.0 to 300 pM proteolytically active human a-thrombin. After 12 hr in thrombin-containing medium, 98% of the astrocytes had a flattened morphology. No flattening occurred if a-thrombin was replaced by y-thrombin, which has its fibrinogen-recognition exosite disrupted. PNI added at 1 nM to serum-containing medium caused stellation after 3 hr, and astroglia were 50% stellate by 12 hr. The effect of thrombin was mimicked by a 7-amino acid peptide (TRP-7) from the cleavage site of the human thrombin receptor. This peptide caused 40% of the astrocytes in serumfree medium to exhibit a flattened morphology after 6 hr. PNI had no effect on TRP-7 action on astrocytes. These results indicate that astrocytes possess a cellsurface receptor for thrombin, similar to that described for platelets, endothelial cells, and neurons.