Evidence that protease-activated receptor-2 mediates trypsin-induced reversal of stellation in cultured rat astrocytes

Gyu Hwan Park, Jae Ryun Ryu, Chan Young Shin, Min Sik Choi, Byoung H. Han, Won-Ki Kim, Hyoung Chun Kim, Ho K. Kwang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Serine proteases such as thrombin and trypsin play a key role in the development and repair processes in the central nervous system. Molecular actions of serine proteases include multiple cellular events like activation of protease-activated receptors (PARs). PARs belong to a family of G protein-coupled receptors that can be stimulated through their proteolytic cleavage by ligands. PAR-2 has been implicated in neurodegenerative diseases including astrogliosis. Although recent studies have shown that low concentration of trypsin activates PAR-2, its role in morphological changes in primary astrocytes has not been studied. In the present study, we investigated the effects of PAR-2 in astrocyte stellation in rat primary astrocyte culture. Both trypsin (0.1-1 U/ml) and a PAR-2-activating peptide SLIGRL-NH2 (1-50 μM) significantly reversed the stellation induced by serum deprivation in rat astrocytes. Treatment of astrocytes with trypsin or SLIGRL-NH2 resulted in a transient rise of the intracellular Ca2+ level and trypsin-induced morphological changes were blocked by BAPTA, a Ca2+ chelator. In addition, a protein kinase C (PKC) inhibitor, bisindolylmaleimide significantly inhibited the trypsin-induced morphological changes, whereas activation of PKC by phorbol-12-myristate-13-acetate acted as trypsin. Taken together, these results suggest that activation of PAR-2 by trypsin caused reversal of stellation in cultured astrocytes, in part, via the mobilization of intracellular Ca2+ and activation of PKC.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalNeuroscience Research
Volume54
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1
Externally publishedYes

Keywords

  • Ca
  • Protease-activated receptor-2
  • Protein kinase C
  • Rat primary astrocyte cultures
  • Reversal of stellation
  • Trypsin

ASJC Scopus subject areas

  • Neuroscience(all)

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