Title details Help Title Effect of ceramide, sphingosine and sphingosine 1-phosphate on the Na+/ K+ ATPase in HepG2 cells / by Zeina Mohammed Dakroub Thesis Name(s) Dakroub, Zeina Mohammed (Main Author) American University of Beirut. Faculty of Arts and Sciences. Department of Biology (Related name) Publication 2009 Link(s) Click for full-text Physical Details xvii, 87 leaves; ill.; 30 cm. Subjects Ceramides Sodium/potassium ATPase Sphingosine Sphingolipids Tumor necrosis factor Classmarks T:005288 Notes Dissertation: Thesis (M.S.)--American University of Beirut, Dept. of Biology, 2009. Dissertation: Advisor : Dr. Sawsan Kuraydiyyah, Professor, Biology Member of Committee : Dr. Elias Baydoun , Professor, Biology Member of Committee : Dr. Khuzama Knio, Professor, Biology. Bib. & Index: Bibliography : leaves 80-87. Abstract TNF-alpha is a pleiotropic cytokine that was previously shown to exert time dependent dual and antagonistic effects on the Na+/ K+-ATPase .It is known to cause the release of the sphingolipid ceramide whose intracellular level plays a central role in the susceptibility of HepG2 cells to TNF-induced apoptosis. Once formed, ceramide enters the sphingomyelin pathway where it gets modified by several enzymes to other sphingolipids such as sphingosine, sphingosine 1-phospate (S1P) and ceramide 1-phospate (C1P) some of which have antagonistic effects to ceramide. The ratio of ceramide to the other sphingolipids determines the final outcome of the cell response. This work was undertaken to study the role of ceramide and its intermediates on the Na+/ K+-ATPase in HepG2 cells and to determine the signaling pathways involved. Cells were incubated for 15min or 2h with ceramide, sphingosine, or S1P in the presence or absence of CAY 10466, SHKI, PDTC and Curcumin, respective inhibitors of ceramidase, spingosine kinasse (SPHK), NF-kappa B and c-JNK. The activity of the pump was assayed by measuring the release of inorganic phosphate in the presence or absence of inhibiting conditions, and changes in its expression were monitored by western blot analysis. At 15min, S1P mediated the down-regulatory effects of ceramide on the Na+/ K+-ATPase. S1P was found to act via an inhibition of NF-kappa B and JNK which activate a certain factor X that in turn stimulates the pump. At 2h, ceramide itself or ceramide 1 phoshate (C1P) was responsible for the up-regulatory effect on the Na+/ K+-ATPase and was shown to act via activation of JNK. NF-kappa B was found to exert an inhibitory effect on the pump at 2 h and was itself inhibited by JNK. Taken together, these data indicate that at early times, the down-regulatory effects are due to S1P and at late times ceramide or C1P mediate the up-regulatory effects on the pump. Availability Barcode Location Shelf Shelfmark Status Category   Jafet Archives and Special Collections Thesis T:5288:c.1 ASC-Binding Building Use

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