title: Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.
abstract: It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9-25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25-50 µm), large aggregates (50-70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.
authors.affiliation: Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi 474-8511, Japan. tokuda@ncgg.go.jp.|Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. tokuda@ncgg.go.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. kokuryugen@yahoo.co.jp.|Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Nagoya 467-8601, Japan. kokuryugen@yahoo.co.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. masanori-t.117@hotmail.co.jp.|Department of Neurosurgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. masanori-t.117@hotmail.co.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. riemn@gifu-u.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Chuno Kosei Hospital, 5-1 Wakakusa, Seki, Gifu 501-6062, Japan. shigeruakamatsu@yahoo.co.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.affiliation: Department of Neurosurgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. enomoto@gifu-u.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. iida@gifu-u.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Nagoya 467-8601, Japan. t.otsuka@med.nagoya-cu.ac.jp.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. oguras@gifu-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Neurosurgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. tiwama@gifu-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.affiliation: Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi 474-8511, Japan. koji-kun@ncgg.go.jp.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. okozawa@gifu-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D018832:Molecular Chaperones; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012402:Rotenone / Q000031:analogs & derivatives / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009842:Oligopeptides; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; C096900:thrombin receptor-activating peptide SFLLRNPNDKY; D012402:Rotenone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C107676:deguelin
keywords: Akt; HSP27; diabetes mellitus; platelet; thrombin-activating protein