title: Ceramide and its metabolites modulate time-dependently the activity of the Na⁺/K⁺ ATPase in HepG2 cells.
abstract: Ceramide is involved in the regulation of many cellular processes including cell proliferation and apoptosis, which are accompanied respectively with a decrease and an increase in the activity of the Na(+)/K(+) ATPase. These antagonistic effects may be time-dependent and due to different signaling pathways requiring different time intervals to be activated. While we showed previously a ceramide-induced inhibition of the ATPase in HepG2 cells during the first hour, we study here the effect of ceramide thereafter. Ceramide stimulated the Na(+)/K(+) ATPase between 1 and 4h with a peak at 2h. This stimulation was maintained in the simultaneous presence of an inhibitor of ceramidase (CAY 10466) but disappeared when ceramide kinase was inhibited, suggesting a role of ceramide-1-phosphate (cer-1-P) in the observed effect. Exogenous cer-1-P caused a similar stimulation of the ATPase which was not affected by an inhibition of JNK but changed into a decrease in presence of PDTC, a specific inhibitor of NF-κB, and disappeared when NF-κB and JNK were inhibited simultaneously. It was concluded that cer-1-P activates both JNK and NF-κB. While JNK exerts an inhibitory effect on the ATPase, NF-κB increases its activity and abrogates the stimulatory effect of the sphingolipid on JNK leading thus to an additional increase in the ATPase activity.
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
authors.affiliation: Department of Biology, Faculty of Arts & Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Dakroub
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D002518:Ceramides; D016328:NF-kappa B; C065576:ceramide 1-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Ceramide; Ceramide one phosphate; JNK; NF-κB; Na(+)/K(+) ATPase