The effects of stimulating protease-activated receptor-1 and -2 in A172 human glioblastoma

T. Okamoto, M. Nishibori, K. Sawada, H. Iwagaki, N. Nakaya, A. Jikuhara, N. Tanaka, K. Saeki

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Human glioblastoma cell line A172 expressed protease-activated receptor-1 and -2 (PAR-1 and PAR-2). We investigated the effects of the stimulation of these receptors by receptor-activating agonist peptides on the Ca2+ signaling, protein kinase C translocation, cell morphology and cell proliferation in A172. Both PAR-1 agonist SFLLRN and PAR-2 agonist SLIGKV induced an increase in [Ca2+]i. The prior treatment of A172 with PAR-2 agonist SLIGKV did not influence the [Ca2+]i response to PAR-1 agonist SFLLRN or thrombin, however, the prior treatment with PAR-1 agonist SFLLRN or thrombin completely abolished the second response to PAR-2 agonist SLIGKV. Treatment with each agonist peptide produced thinner and fewer processes in A172. The PAR-2 agonist inhibited the proliferation of A172 significantly while PAR-1 agonist did not. PKC-α and γ were translocated from cytosol to membrane with either PAR-1 or PAR-2 stimulation, however, ι was specifically translocated with SFLLRN, and λ with SLIGKV, respectively. These results indicated that PAR-1 and PAR-2 stimulation produced a similar [Ca2+]i response and morphological changes in A172 glioblastoma while the effects on the cell proliferation and activation of PKC isozymes were distinct, suggesting that different signal transduction pathways were activated by these receptors. The uni-directional cross desensitization implies a functional linkage between PAR-1 and PAR-2 receptors.

Original languageEnglish
Pages (from-to)125-140
Number of pages16
JournalJournal of Neural Transmission
Volume108
Issue number2
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • A172 glioblastoma
  • Calcium signal
  • Proliferation
  • Protease-activated receptor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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