Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK
Background/Aims: 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. We previously reported that phosphorylated-heat shock protein 27 (HSP27) is released from t...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-09-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/493456 |
| _version_ | 1811286066810847232 |
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| author | Kodai Uematsu Yukiko Enomoto Takashi Onuma Masanori Tsujimoto Tomoaki Doi Rie Matsushima-Nishiwaki Haruhiko Tokuda Shinji Ogura Hiroki Iida Osamu Kozawa Toru Iwama |
| author_facet | Kodai Uematsu Yukiko Enomoto Takashi Onuma Masanori Tsujimoto Tomoaki Doi Rie Matsushima-Nishiwaki Haruhiko Tokuda Shinji Ogura Hiroki Iida Osamu Kozawa Toru Iwama |
| author_sort | Kodai Uematsu |
| collection | DOAJ |
| description | Background/Aims: 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. We 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, we investigated the role of Rac in the TRAP-elicited release of phosphorylated-HSP27 from human platelets. Methods: 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. Results: 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: Our 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. |
| first_indexed | 2024-04-13T02:54:02Z |
| format | Article |
| id | doaj.art-83136f285ed541e0bd927e4757da2f47 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T02:54:02Z |
| publishDate | 2018-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-83136f285ed541e0bd927e4757da2f472022-12-22T03:05:44ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014941523153810.1159/000493456493456Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNKKodai UematsuYukiko EnomotoTakashi OnumaMasanori TsujimotoTomoaki DoiRie Matsushima-NishiwakiHaruhiko TokudaShinji OguraHiroki IidaOsamu KozawaToru IwamaBackground/Aims: 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. We 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, we investigated the role of Rac in the TRAP-elicited release of phosphorylated-HSP27 from human platelets. Methods: 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. Results: 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: Our 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.https://www.karger.com/Article/FullText/493456PlateletRacp38 MAP kinaseJNKProtease-activated receptorThrombin receptor-activating peptideHeat shock protein 27Phosphorylation |
| spellingShingle | Kodai Uematsu Yukiko Enomoto Takashi Onuma Masanori Tsujimoto Tomoaki Doi Rie Matsushima-Nishiwaki Haruhiko Tokuda Shinji Ogura Hiroki Iida Osamu Kozawa Toru Iwama Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK Cellular Physiology and Biochemistry Platelet Rac p38 MAP kinase JNK Protease-activated receptor Thrombin receptor-activating peptide Heat shock protein 27 Phosphorylation |
| title | Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK |
| title_full | Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK |
| title_fullStr | Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK |
| title_full_unstemmed | Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK |
| title_short | Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human Platelets via p38 MAP Kinase but Not JNK |
| title_sort | rac regulates the trap induced release of phosphorylated hsp27 from human platelets via p38 map kinase but not jnk |
| topic | Platelet Rac p38 MAP kinase JNK Protease-activated receptor Thrombin receptor-activating peptide Heat shock protein 27 Phosphorylation |
| url | https://www.karger.com/Article/FullText/493456 |
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