SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets

Autor:	Chulhun L. Chang, In Suk Kim, Jin Ung Bae, Chi Dae Kim, Sae-Ock Oh, Yun Hak Kim
Rok vydání:	2016
Předmět:	Blood Platelets Lung Diseases 0301 basic medicine Platelet Aggregation Platelet Function Tests Receptor expression Down-Regulation Platelet Membrane Glycoproteins Pulmonary Artery Pharmacology Platelet membrane glycoprotein Receptors G-Protein-Coupled Mice 03 medical and health sciences chemistry.chemical_compound Thrombin Sirtuin 1 Downregulation and upregulation medicine Animals Humans Platelet Thrombus Arachidonic Acid Platelet-activating factor Thrombosis Hematology General Medicine medicine.disease Cell aggregation 030104 developmental biology Gene Expression Regulation chemistry Biochemistry lipids (amino acids peptides and proteins) medicine.drug
Zdroj:	Platelets. 27:735-742
ISSN:	1369-1635 0953-7104
Popis:	SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH4Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e15947be69688fcb8de839f8ca54c0d https://doi.org/10.1080/09537104.2016.1190005 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.