Small molecular weight heat shock-related protein, HSP20, exhibits an anti-platelet activity by inhibiting receptor-mediated calcium influx.
We have shown that Hsp20, one of small molecular weight heat shock protein, which is present at a high concentration both in vascular smooth muscle cells and in circulating blood in patient with vascular disease, strongly inhibits platelet aggregation in vitro and ex vivo. To clarify the mechanism, we investigated the effect of Hsp20 on free calcium concentration in human platelet cytoplasm using fura 2. Hsp20 inhibited thrombin-induced calcium influx without affecting calcium release from intracellular calcium stores. The degree of inhibition is well-correlated with that of suppression of thrombin-induced platelet aggregation by this substance. Hsp20 also inhibited the elevation of cytoplasmic free calcium level triggered by collagen, but not that by A-23187. In contrast, Hsp28, another type of small molecular weight Hsp, failed to affect the cytoplasmic free calcium level. These findings suggest that Hsp20 inhibits the receptor-mediated calcium influx of platelets without affecting calcium release from intracellular calcium stores, leading to its anti-platelet activity.
Niwa
M
M
Department of Pharmacology, Gifu University School of Medicine, Japan. mniwa@cc.gifu-u.ac.jp
Kozawa
O
O
Matsuno
H
H
Kato
K
K
Uematsu
T
T
D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008970:Molecular Weight; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism
D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D007476:Ionophores; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000001:Calcimycin; D003094:Collagen; D013917:Thrombin; D002118:Calcium