HSP20, low-molecular-weight heat shock-related protein, acts extracellularly as a regulator of platelet functions: a novel defense mechanism.
We previously showed that a dissociated form of a low-molecular-weight heat shock-related protein 20 (HSP20) but not an aggregated form of HSP20 suppresses platelet aggregation. In the present study, we investigated the behavior of HSP20 in response to endothelial injury and the possible mechanism of HSP20 in platelet functions. The levels of HSP20 in vessel wall after endothelial injury were markedly reduced. This observation was supported by the results of Western blotting analysis and immunohistochemical analysis. Additionally, the plasma levels of HSP20 in cardiomyopathic hamsters were markedly elevated. Centrifugation on sucrose density gradients allowed detection mainly of the dissociated form of plasma HSP20 in these hamsters. Human platelets showed specific binding sites for HSP20. Moreover, HSP20 markedly reduced thrombin-induced phosphoinositide hydrolysis by phospholipase C in human platelets. Taken together, our results strongly suggest that HSP20, which immediately responds to pathological events, acts extracellularly as a regulator of platelet functions.
Kozawa
Osamu
O
Department of Pharmacology, Gifu University, School of Medicine, 500-8705, Gifu, Japan. okozawa@cc.gifu-u.ac.jp
Matsuno
Hiroyuki
H
Niwa
Masayuki
M
Hatakeyama
Daijiro
D
Oiso
Yutaka
Y
Kato
Kanefusa
K
Uematsu
Toshihiko
T
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology*; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology; D005110:Extracellular Space / Q000502:physiology; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010979:Platelet Function Tests; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry; D010738:Type C Phospholipases / Q000097:blood
D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D007294:Inositol; D010738:Type C Phospholipases; D013917:Thrombin