title: Leptin inhibits the Na(+)/K(+) ATPase in Caco-2 cells via PKC and p38MAPK.
abstract: We demonstrated previously an inhibitory effect of luminal leptin on glucose absorption in differentiated Caco-2 cells. Since this process is dependent on the Na(+) gradient established by the Na(+)/K(+)ATPase this work was undertaken to investigate if the ATPase is one of the hormone's targets. Fully differentiated Caco-2 cells were incubated with 10nM luminal leptin and the activity of the Na(+)/K(+) ATPase was assayed by measuring the amount of inorganic phosphate liberated. To elucidate the signaling pathway involved, the suspected mediators, namely PKC, p38MAPK, ERK and PI3K, were inhibited with specific pharmacological inhibitors and their implication was confirmed by determining changes in the protein expression of their active phosphorylated forms by Western blot analysis. Leptin reduced significantly the activity of the Na(+)/K(+) ATPase, by activating p38MAPK via inhibition of PKC, an upstream inhibitor of the kinase. ERK and PI3K are modulators of the pump and are not along the pathway activated by leptin but cross talk with it at the level of p38MAPK.
authors.affiliation: Department of Biology, Faculty of Arts & Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Ola
authors.initials: O
authors.lastname: El-Zein
authors.affiliation: Department of Biochemistry & Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Julnar
authors.initials: J
authors.lastname: Usta
authors.affiliation: Department of Biology, Faculty of Arts & Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Layla
authors.initials: L
authors.lastname: El Moussawi
authors.affiliation: Department of Biology, Faculty of Arts & Sciences, American University of Beirut, Beirut, Lebanon. Electronic address: Sawkreyd@aub.edu.lb.
authors.forename: Sawsan Ibrahim
authors.initials: SI
authors.lastname: Kreydiyyeh
mesh_terms: D018938:Caco-2 Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Caco-2; Leptin; Na(+)/K(+)ATPase; PKC; p38MAPK