Your browser doesn't support javascript.
loading
Transient receptor potential channel 1 maintains adherens junction plasticity by suppressing sphingosine kinase 1 expression to induce endothelial hyperpermeability.
Tauseef, Mohammad; Farazuddin, Mohammad; Sukriti, Sukriti; Rajput, Charu; Meyer, James Otto; Ramasamy, Suresh Kumar; Mehta, Dolly.
Afiliación
  • Tauseef M; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Farazuddin M; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Sukriti S; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Rajput C; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Meyer JO; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Ramasamy SK; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA.
  • Mehta D; Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA dmehta@uic.edu.
FASEB J ; 30(1): 102-10, 2016 Jan.
Article en En | MEDLINE | ID: mdl-26316271
Stability of endothelial cell (EC) adherens junctions (AJs) is central for prevention of tissue edema, the hallmark of chronic inflammatory diseases including acute respiratory distress syndrome. Here, we demonstrate a previously unsuspected role of sphingosine kinase 1 (SPHK1) in the mechanism by which transient receptor potential channel 1 (Trpc1)-mediated Ca(2+) entry destabilizes AJs. Trpc1(-/-) monolayers showed a 2.2-fold increase in vascular endothelial (VE)-cadherin cell-surface expression above wild-type (WT) monolayers. Thrombin increased endothelial permeability (evident by a 5-fold increase in interendothelial gap area and 60% decrease in transendothelial electrical resistance) in WT but not Trpc1(-/-) ECs. Trpc1(-/-) mice resisted the hyperpermeability effects of the edemagenic agonists used and exhibited 60% less endotoxin-induced mortality. Because sphingosine-1-phosphate (S1P) strengthens AJs, we determined if TRPC1 functioned by inhibiting SPHK1 activity, which generates S1P. Intriguingly, Trpc1(-/-) ECs or ECs transducing a TRPC1-inactive mutant showed a 1.5-fold increase in basal SPHK1 expression compared with WT ECs, resulting in a 2-fold higher S1P level. SPHK1 inhibitor SK1-I decreased basal transendothelial electrical resistance more in WT ECs (48 and 72% reduction at 20 and 50 µM, respectively) than in Trpc1(-/-) ECs. However, SK1-I pretreatment rescued thrombin-induced EC permeability in Trpc1(-/-) ECs. Thus, TRPC1 suppression of basal SPHK1 activity enables EC-barrier destabilization by edemagenic agonists.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfotransferasas (Aceptor de Grupo Alcohol) / Uniones Adherentes / Células Endoteliales / Endotelio / Canales Catiónicos TRPC Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfotransferasas (Aceptor de Grupo Alcohol) / Uniones Adherentes / Células Endoteliales / Endotelio / Canales Catiónicos TRPC Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos