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24 janvier 2025
- 10938/25049
- 27501354.0
- 2-s2.0-84982104739
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Biochemistry and Cell Biology
Mots-clés
Fty720p Hepg2 Na+-k+atpase Nf-κb Pge2 Pkc S1pr2 Blotting, western Carcinoma, hepatocellular Dinoprostone Humans Liver neoplasms Lysophospholipids Nf-kappa b Organophosphates Protein kinase c Receptors, lysosphingolipid Sodium-potassium-exchanging atpase Sphingosine Tumor cells, cultured Sphingosines Adenosine triphosphatase (potassium sodium) inhibitor Calphostin Fty 720p Immunoglobulin enhancer binding protein Indometacin Phorbol 13 acetate 12 myristate Prostaglandin e2 Sphingosine 1 phosphate Unclassified drug Adenosine triphosphatase (potassium sodium) Lysophospholipid Organophosphate S1pr2 protein, human Sphingosine 1 phosphate receptor Sphingosine 1-phosphate Inorganic phosphates Mechanism of action Article Controlled study Drug effect Drug mechanism Enzyme inhibition Gene expression Hepg2 cell line Human Human cell In vitro study Signal transduction Analogs and derivatives Antagonists and inhibitors Metabolism Pathology Tumor cell culture Western blotting SodiumSujets proches
Adenosinetriphosphatase ATPase Adenylopyrophosphatase ATP monophosphatase ATP synthetase ATP synthase ATP phosphohydrolaseCiter ce document
Al Alam et al., « FTY720P inhibits hepatic Na+-K+ ATPase via S1PR2 and PGE2 », American University of Beirut ScholarWorks
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Résumé
Sphingosine-1-phosphate (S1P) was found previously to inhibit Na+-K+ ATPase in HepG2 cells. Whether fingolimod (FTY720), a S1P receptor (S1PR) agonist, similarly inhibits the ATPase is a question that needs to be addressed. The aim of this work was to study the effect of FTY720P, the active form of the drug, on the activity of Na+-K+ ATPase in HepG2 cells and determine its mechanism of action. The activity of the ATPase was assayed by measuring the amount of inorganic phosphate liberated in the presence and the absence of ouabain. FTY720-P (7.5 nmol/L, 15 min) significantly reduced the activity of the ATPase. This effect disappeared completely in the presence of JTE-013, which is a specific blocker of sphingosine-1-phosphate receptor 2 (S1PR2), as well as in the presence of calphostin and indomethacin, which are inhibitors of protein kinase C (PKC) and COX-2, respectively. The effect of FTY720P was mimicked by prostaglandin E2 (PGE2) and PMA, but abrogated by NF-κB inhibition. When NF-κB was inhibited, the effect of exogenous PGE2 still appeared, but that of PMA did not manifest, suggesting that NF-κB is upstream of PGE2 and downstream of PKC. It was concluded that FTY720P activates via S1PR2, PKC, and NF-κB. The latter induces PGE2 generation and inhibits Na+-K+ ATPase. © 2016 Published by NRC Research Press.
