FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4236693852> ?p ?o ?g. }

• W4236693852 abstract "Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in multiple biological processes; it is stored in platelets and released upon activation. Although S1P is known to exert extracellular effects on platelets such as shape change and aggregation, the receptor that mediates these effects and the molecular mechanisms involved are poorly understood. The aim of the present study was to characterize the S1P receptor expressed in platelets as well as the molecular mechanism underlying S1P-mediated platelet activation and eventual changes associated with the development of type 2 diabetes. We found that washed human platelets from healthy volunteers expressed mainly the S1P2 receptor and to a lesser extent the S1P1 receptor. Stimulation of these platelets with exogenous S1P led to a concentration-dependent increase in intracellular calcium as well as to platelet aggregation. The latter response was accompanied by the translocation of RhoA to the membrane and was inhibited (by 50%, P<0.01) by the Rho kinase inhibitor Y27632 (1 μmol/L). Neither the PKC inhibitor, Ro-318220, the MAPK inhibitor, PD98059, nor the tyrosine kinase inhibitor, tyrphostin A-23, affected the S1P-mediated platelet aggregation. Serum obtained from patients with type 2 diabetes contained 1.5-fold higher levels (P<0.01) of S1P that from healthy individuals. However, platelets from patients with type 2 diabetes demonstrated an attenuated aggregability to S1P as well as decreased levels of the S1P2 protein. The latter was found to be a target of the calcium-dependent protease μ-calpain which we found to be highly activated in platelets from patients with type 2 diabetes. Finally, stimulation of platelets from healthy donors with high concentration of S1P led to the activation of μ-calpain. Taken together, our results show that S1P can elicit platelet aggregation by activating the S1P2 receptor and the RhoA-Rho kinase pathway. In platelets from patients with type 2 diabetes, in which the circulating concentration of S1P is elevated, responses to S1P are damped, via a phenomenon that correlates with the activation of μ-calpain and the subsequent degradation of the S1P2 receptor. The latter may represent an auto-protective mechanism against exaggerated platelet activation in diabetes." @default.
• W4236693852 created "2022-05-12" @default.
• W4236693852 creator A5025448215 @default.
• W4236693852 creator A5050471583 @default.
• W4236693852 creator A5080822146 @default.
• W4236693852 creator A5091173895 @default.
• W4236693852 date "2007-10-16" @default.
• W4236693852 modified "2023-10-18" @default.
• W4236693852 title "Abstract 453: The S1p2 Receptor Is Expressed In Human Platelets,is Linked To The Rhoa-rho Kinase Pathway And Is Degraded By μ-calpain In Type 2 Diabetes" @default.
• W4236693852 doi "https://doi.org/10.1161/circ.116.suppl_16.ii_76" @default.
• W4236693852 hasPublicationYear "2007" @default.
• W4236693852 type Work @default.
• W4236693852 citedByCount "0" @default.
• W4236693852 crossrefType "journal-article" @default.
• W4236693852 hasAuthorship W4236693852A5025448215 @default.
• W4236693852 hasAuthorship W4236693852A5050471583 @default.
• W4236693852 hasAuthorship W4236693852A5080822146 @default.
• W4236693852 hasAuthorship W4236693852A5091173895 @default.
• W4236693852 hasConcept C126322002 @default.
• W4236693852 hasConcept C134018914 @default.
• W4236693852 hasConcept C149577978 @default.
• W4236693852 hasConcept C170493617 @default.
• W4236693852 hasConcept C181199279 @default.
• W4236693852 hasConcept C184235292 @default.
• W4236693852 hasConcept C2776549689 @default.
• W4236693852 hasConcept C2776596873 @default.
• W4236693852 hasConcept C2777093181 @default.
• W4236693852 hasConcept C2777292125 @default.
• W4236693852 hasConcept C2778703144 @default.
• W4236693852 hasConcept C3018697912 @default.
• W4236693852 hasConcept C55493867 @default.
• W4236693852 hasConcept C56928146 @default.
• W4236693852 hasConcept C62478195 @default.
• W4236693852 hasConcept C71924100 @default.
• W4236693852 hasConcept C86803240 @default.
• W4236693852 hasConcept C89560881 @default.
• W4236693852 hasConcept C95444343 @default.
• W4236693852 hasConceptScore W4236693852C126322002 @default.
• W4236693852 hasConceptScore W4236693852C134018914 @default.
• W4236693852 hasConceptScore W4236693852C149577978 @default.
• W4236693852 hasConceptScore W4236693852C170493617 @default.
• W4236693852 hasConceptScore W4236693852C181199279 @default.
• W4236693852 hasConceptScore W4236693852C184235292 @default.
• W4236693852 hasConceptScore W4236693852C2776549689 @default.
• W4236693852 hasConceptScore W4236693852C2776596873 @default.
• W4236693852 hasConceptScore W4236693852C2777093181 @default.
• W4236693852 hasConceptScore W4236693852C2777292125 @default.
• W4236693852 hasConceptScore W4236693852C2778703144 @default.
• W4236693852 hasConceptScore W4236693852C3018697912 @default.
• W4236693852 hasConceptScore W4236693852C55493867 @default.
• W4236693852 hasConceptScore W4236693852C56928146 @default.
• W4236693852 hasConceptScore W4236693852C62478195 @default.
• W4236693852 hasConceptScore W4236693852C71924100 @default.
• W4236693852 hasConceptScore W4236693852C86803240 @default.
• W4236693852 hasConceptScore W4236693852C89560881 @default.
• W4236693852 hasConceptScore W4236693852C95444343 @default.
• W4236693852 hasIssue "suppl_16" @default.
• W4236693852 hasLocation W42366938521 @default.
• W4236693852 hasOpenAccess W4236693852 @default.
• W4236693852 hasPrimaryLocation W42366938521 @default.
• W4236693852 hasRelatedWork W1982044900 @default.
• W4236693852 hasRelatedWork W2011307558 @default.
• W4236693852 hasRelatedWork W2058889969 @default.
• W4236693852 hasRelatedWork W2059880344 @default.
• W4236693852 hasRelatedWork W2064688542 @default.
• W4236693852 hasRelatedWork W2481038056 @default.
• W4236693852 hasRelatedWork W2897308664 @default.
• W4236693852 hasRelatedWork W2997627044 @default.
• W4236693852 hasRelatedWork W3015148478 @default.
• W4236693852 hasRelatedWork W4236693852 @default.
• W4236693852 hasVolume "116" @default.
• W4236693852 isParatext "false" @default.
• W4236693852 isRetracted "false" @default.
• W4236693852 workType "article" @default.