Reciprocal Modulation of Astrocyte Stellation by Thrombin and Protease Nexin‐1

Reciprocal Modulation of Astrocyte Stellation by Thrombin and Protease Nexin‐1 Abstract: When cultured astroglia are treated with agents that elevate intracellular cyclic AMP, they become process‐bearing stellate cells and resemble differentiated astrocytes in vivo. Thrombin rapidly reversed the stellation induced by dibutyryl cyclic AMP, forskolin, or isoproterenol in cultured rat astrocytes; half‐maximal and maximal effects occurred at 0.5 and 8 pM, respectively. The proteolytic activity of thrombin was required for stellation reversal, as thrombin derivatized at its catalytic site serine with a diisopropylphospho group was inactive. Two thrombin inhibitors, protease nexin‐1 and hirudin, blocked and reversed the effect of thrombin. The stellation reversal effect of thrombin was specific, as 300–1,000‐fold higher concentrations of other serine proteinases, including plasmin, urokinase, trypsin, and T cell serine proteinase‐1, were ineffective. Thrombin is a mitogen for astrocytes at concentrations in excess of 30 pM. Thrombin increased both cell number and ornithine decarboxylase activity, an early marker for mitogenic stimulation, in astrocyte cultures. The lowest thrombin concentrations that completely reversed astrocyte stellation, however, did not increase ornithine decarboxylase activity. Moreover, several other mitogens for astrocytes did not reverse dibutyryl cyclic AMP‐induced stellation. Thus, the stellation reversal effect of thrombin is distinct from the mitogenic response. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Reciprocal Modulation of Astrocyte Stellation by Thrombin and Protease Nexin‐1

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Publisher
Wiley
Copyright
Copyright © 1990 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
DOI
10.1111/j.1471-4159.1990.tb01228.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: When cultured astroglia are treated with agents that elevate intracellular cyclic AMP, they become process‐bearing stellate cells and resemble differentiated astrocytes in vivo. Thrombin rapidly reversed the stellation induced by dibutyryl cyclic AMP, forskolin, or isoproterenol in cultured rat astrocytes; half‐maximal and maximal effects occurred at 0.5 and 8 pM, respectively. The proteolytic activity of thrombin was required for stellation reversal, as thrombin derivatized at its catalytic site serine with a diisopropylphospho group was inactive. Two thrombin inhibitors, protease nexin‐1 and hirudin, blocked and reversed the effect of thrombin. The stellation reversal effect of thrombin was specific, as 300–1,000‐fold higher concentrations of other serine proteinases, including plasmin, urokinase, trypsin, and T cell serine proteinase‐1, were ineffective. Thrombin is a mitogen for astrocytes at concentrations in excess of 30 pM. Thrombin increased both cell number and ornithine decarboxylase activity, an early marker for mitogenic stimulation, in astrocyte cultures. The lowest thrombin concentrations that completely reversed astrocyte stellation, however, did not increase ornithine decarboxylase activity. Moreover, several other mitogens for astrocytes did not reverse dibutyryl cyclic AMP‐induced stellation. Thus, the stellation reversal effect of thrombin is distinct from the mitogenic response.

Journal

Journal of NeurochemistryWiley

Published: May 1, 1990

References

  • Localization of protease nexin‐1 on the fibroblast extracellular matrix
    Farrell, Farrell; Wagner, Wagner; Yuan, Yuan; Cunningham, Cunningham
  • High‐affinity uptake of ( 3 H)norepinephrine by primary astrocyte cultures and its inhibition by tricyclic antidepressant
    Kimelberg, Kimelberg; Pelton, Pelton
  • Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue
    McCarthy, McCarthy; Vellis, Vellis
  • Comparative ultrastructural study of the effects of serum‐free medium and dibutyryl cyclic AMP on newborn rat astroblasts
    Moonen, Moonen; Heinen, Heinen; Goessens, Goessens
  • Effects of norepinephrine on the morphology and some enzyme activities of primary monolayer cultures from rat brain
    Narumi, Narumi; Kimelberg, Kimelberg; Bourke, Bourke
  • Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres
    Schousboe, Schousboe; Svenneby, Svenneby; Hertz, Hertz
  • Morphology of astroglial cells is controlled by beta‐adrenergic receptors
    Shain, Shain; Forman, Forman; Madelian, Madelian; Turner, Turner

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