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Positive regulation of tumor necrosis factor-alpha by ganglioside GM3 through Akt in mouse melanoma B16 cells. 2007

Pu Wang, and Peixing Wu, and Jinghai Zhang, and Toshinori Sato, and Sadako Yamagata, and Tatsuya Yamagata
Laboratory of Tumor Biology and Glycobiology, P.O. Box 29, Shenyang Pharmaceutical University, 103 WenHua Road, Shenyang 110016, People's Republic of China.

GM3 has been shown to suppress TNFalpha expression in blood monocytes. However, we found that GM3 and TNFalpha were expressed in parallel in mouse melanoma B16 cells that were transfected with UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase cDNA in a sense or antisense direction or CMP-NeuAc:lactosylceramide alpha-2,3-sialyltransferase siRNA. TNFalpha expression was increased by addition of GM3 to the B16 transfectants and decreased after treatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthesis. These results clearly indicate that GM3 positively regulates TNFalpha expression in B16 cells. Phosphoinositide 3-kinase inhibitors, wortmannin and LY294,002, suppressed TNFalpha expression and Akt phosphorylation. GM3 was shown to increase phosphorylation of Akt in B16 cells and the B16-derived transfectants. Treatment of B16 cells with siRNA targeted to Akt1/2 resulted in TNFalpha suppression, indicating that Akt plays an important role in regulation of TNFalpha expression. Suppression of Akt1/2 rendered cells insensitive to GM3, suggesting that the GM3 signal may be transduced via Akt.

UI MeSH Term Description Entries
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D009025 Morpholines Tetrahydro-1,4-Oxazines,Tetrahydro 1,4 Oxazines
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D002867 Chromones 1,4-Benzopyrones,Chromone,1,4 Benzopyrones
D005679 G(M3) Ganglioside A ganglioside present in abnormally large amounts in the brain and liver due to a deficient biosynthetic enzyme, G(M3):UDP-N-acetylgalactosaminyltransferase. Deficiency of this enzyme prevents the formation of G(M2) ganglioside from G(M3) ganglioside and is the cause of an anabolic sphingolipidosis. Hematoside,Sialyllactosylceramide,Ganglioside GM3,II3NeuAcLacCer,Sialyl Lactosylceramide,GM3, Ganglioside,Lactosylceramide, Sialyl
D000077191 Wortmannin An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential. MS 54,MS-54,MS54
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D000730 Androstadienes Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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