Recombinant protein 1/secretoglobin 1A1 participates in the actin polymerization of human platelets.
BACKGROUND
Human protein 1 which was originally isolated from pathological urine is identified with clara cell 10 kDa protein and uteroglobin. It has immunomodulatory and anti-inflammatory effects in many vertebrates. Although there have been thorough studies on the structure, molecular biology and biochemical characteristics, the precise mechanism of its biological activities is unknown. The purpose of this research is to clarify the biochemical mechanism of protein 1 through its effect on the platelet aggregation process.


METHODS
Changes in calcium mobilization, actin filament concentrations and functions of integrin alphaIIbbeta3 resulting from platelet stimulation were measured in the presence or absence of recombinant protein 1 (rP1).


RESULTS
Recombinant protein 1 inhibited U46619- and thapsigargin-induced platelet aggregation by preventing store mediated calcium entry (SMCE). The binding of rP1 to resting platelets induced an increase in the actin filament that accompanied the structural changes of alphaIIbbeta3. When rP1-pretreated platelets were activated by thrombin or thapsigargin, the alterations in the actin filament and alphaIIbbeta3 resulting from the stimulation decreased.


CONCLUSIONS
These results suggest that rP1 inhibits platelet aggregation by participation in the actin polymerization through which SMCE is mediated.
Hayashi
Yukiko
Y
Department of Laboratory Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan. yuhayasi@asahikawa-med.ac.jp
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins; D019284:Thapsigargin / Q000494:pharmacology; D014598:Uteroglobin
D000199:Actins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011506:Proteins; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; D019284:Thapsigargin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014598:Uteroglobin; D002118:Calcium