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

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• 作者：Gyu Hwan Park ; Jae Ryun Ryu ; Chan Young Shin ; Min Sik Choi ; Byoung-Hee Han ; Won-Ki Kim ; Hyoung-Chun Kimand Kwang Ho Ko
• 关键词：Trypsin ; Protease-activated receptor-2 ; Reversal of stellation ; Rat primary astrocyte cultures ; Ca²⁺ ; Protein kinase C
• 刊名：Neuroscience Research
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：54
• 期：1
• 页码：15-23
• 全文大小：381 K

文摘

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.