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 Hee Han, Won Ki Kim, Hyoung Chun Kim, Ho Ko 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
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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