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Protease activated receptor

Thrombin induces the activation of human platelets through protease activated receptor (PAR) 1 and PAR4, and Rac, a member of the Rho family of small GTPases, is implicated in PAR activation.

Uematsu et al. from the Gifu University Graduate School of Medicine, Japan, previously reported that phosphorylated-heat shock protein 27 (HSP27) is released from the thrombin receptor-activating peptide (TRAP)-stimulated platelets of diabetic patients. In the present study, they investigated the role of Rac in the TRAP-elicited release of phosphorylated-HSP27 from human platelets.

Platelet aggregation was measured using an aggregometer with laser scattering. Protein phosphorylation was analyzed by Western blotting. The levels of phosphorylated-HSP27 and platelet-derived growth factor-AB (PDGF-AB) were measured by enzyme-linked immunosorbent assays.

NSC23766, an inhibitor of Rac-guanine nucleotide exchange factor interaction, suppressed the TRAP-elicited release of phosphorylated-HSP27 as well as platelet aggregation. The TRAP-induced phosphorylation of HSP27, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was attenuated by NSC23766. SB203580, a p38 MAPK inhibitor, but not SP600125, a JNK inhibitor, suppressed the release of phosphorylated-HSP27 in addition to HSP27 phosphorylation. On the other hand, both SB203580 and SP600125 reduced the TRAP-stimulated secretion of PDGF-AB. CONCLUSION:

The results strongly suggest that Rac acts as a positive regulator of the PAR-elicited release of phosphorylated-HSP27 from human platelets via p38 MAPK but not JNK 1).

Uematsu K, Enomoto Y, Onuma T, Tsujimoto M, Doi T, Matsushima-Nishiwaki R, Tokuda H, Ogura S, Iida H, Kozawa O, Iwama T. Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK. Cell Physiol Biochem. 2018 Sep 13;49(4):1523-1538. doi: 10.1159/000493456. [Epub ahead of print] PubMed PMID: 30212812.
protease_activated_receptor.txt · Last modified: 2018/09/14 12:06 by administrador