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The transmembrane protein disulfide isomerase TMX1 negatively regulates platelet responses.
Zhao, Zhenzhen; Wu, Yi; Zhou, Junsong; Chen, Fengwu; Yang, Aizhen; Essex, David W.
Afiliação
  • Zhao Z; The Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhow, China; and.
  • Wu Y; The Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhow, China; and.
  • Zhou J; Sol Sherry Thrombosis Research Center, Division of Hematology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA.
  • Chen F; The Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhow, China; and.
  • Yang A; Sol Sherry Thrombosis Research Center, Division of Hematology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA.
  • Essex DW; The Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhow, China; and.
Blood ; 133(3): 246-251, 2019 01 17.
Article em En | MEDLINE | ID: mdl-30425049
Secreted platelet protein disulfide isomerases, PDI, ERp57, ERp5, and ERp72, have important roles as positive regulators of platelet function and thrombosis. Thioredoxin-related transmembrane protein 1 (TMX1) was the first described transmembrane member of the protein disulfide isomerase family of enzymes. Using a specific antibody, the recombinant extracellular domain of TMX1 (rTMX1) protein, a knockout mouse model, and a thiol-labeling approach, we examined the role of TMX1 in platelet function and thrombosis. Expression of TMX1 on the platelet surface increased with thrombin stimulation. The anti-TMX1 antibody increased platelet aggregation induced by convulxin and thrombin, as well as potentiated platelet ATP release. In contrast, rTMX1 inhibited platelet aggregation and ATP release. TMX1-deficient platelets had increased aggregation, ATP release, αIIbß3 activation, and P-selectin expression, which were reversed by addition of rTMX1. TMX1-knockout mice had increased incorporation of platelets into a growing thrombus in an FeCl3-induced mesenteric arterial injury model, as well as shortened tail-bleeding times. rTMX1 oxidized thiols in the αIIbß3 integrin and TMX1-deficient platelets had increased thiols in the ß3 subunit of αIIbß3, consistent with oxidase activity of rTMX1 against αIIbß3. Thus, TMX1 is the first identified extracellular inhibitor of platelet function and the first disulfide isomerase that negatively regulates platelet function.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiorredoxinas / Trombose / Plaquetas / Ativação Plaquetária / Agregação Plaquetária / Complexo Glicoproteico GPIIb-IIIa de Plaquetas / Proteínas de Membrana Limite: Animals / Humans Idioma: En Revista: Blood Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiorredoxinas / Trombose / Plaquetas / Ativação Plaquetária / Agregação Plaquetária / Complexo Glicoproteico GPIIb-IIIa de Plaquetas / Proteínas de Membrana Limite: Animals / Humans Idioma: En Revista: Blood Ano de publicação: 2019 Tipo de documento: Article