title: Significant correlation between the acceleration of platelet aggregation             and phosphorylation of HSP27 at Ser-78 in diabetic patients.
abstract: To clarify the mechanism underlying a high risk of thrombotic complications in diabetic patients, we investigated the relationship between HSP27 phosphorylation and the platelet activation induced by adenosine diphosphate (ADP) in diabetic patients. Platelet-rich plasma was prepared from the blood of type 2 diabetes mellitus (DM) patients. By measuring the dose response of platelet aggregation to ADP, an individual ED50 was determined. Based on the normal range identified in non-DM controls, the subjects were divided into a hyper-aggregate (Group 1) and a normo- or hypo-aggregate group (Group 2). The protein phosphorylation was analyzed by western blotting. The release of PDGF-AB and sCD40 ligand (sCD40L) was measured by ELISA. In both groups, ADP induced HSP27 phosphorylation at Ser-78 and Ser-82. The phosphorylation at Ser-78 and the release of both PDGF-AB and sCD40L induced by a low dose of ADP (1 µM) in Group 1 were significantly higher than these values in Group 2. There was a significant relationship between the ADP-induced HSP27 phosphorylation level at Ser-78 and the ADP ED50 value of platelet aggregation. The ADP (1 µM)-induced phosphorylation of HSP at Ser-78 observed in the platelets from Group 1 was inhibited by PD98059 or SB203580. The use of aspirin ameliorated the accelerated microaggregation of platelets in Group 1, and the low-dose ADP-induced phosphorylation of HSP27 at Ser-78 was no longer observed. These results strongly suggest that the phosphorylation of HSP27 at Ser-78 is correlated with the acceleration of platelet aggregation induced by ADP in type 2 DM patients.
authors.affiliation: Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. tokuda@ncgg.go.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Senji
authors.initials: S
authors.lastname: Kasahara
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Mizuno
authors.forename: Seiko
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology / Q000502:physiology; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018832:Molecular Chaperones; D010766:Phosphorylation; D010974:Platelet Aggregation; D011499:Protein Processing, Post-Translational; D011725:Pyridines / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D005419:Flavonoids; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D007093:Imidazoles; D018832:Molecular Chaperones; D011725:Pyridines; D023201:CD40 Ligand; D012694:Serine; D000244:Adenosine Diphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one