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

Pu Wang, Peixing Wu, Jinghai Zhang, Toshinori Sato, Sadako Yamagata, Tatsuya Yamagata

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

GM3 has been shown to suppress TNFα expression in blood monocytes. However, we found that GM3 and TNFα were expressed in parallel in mouse melanoma B16 cells that were transfected with UDP-Gal:glucosylceramide β-1,4-galactosyltransferase cDNA in a sense or antisense direction or CMP-NeuAc:lactosylceramide α-2,3-sialyltransferase siRNA. TNFα 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 TNFα expression in B16 cells. Phosphoinositide 3-kinase inhibitors, wortmannin and LY294,002, suppressed TNFα 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 TNFα suppression, indicating that Akt plays an important role in regulation of TNFα expression. Suppression of Akt1/2 rendered cells insensitive to GM3, suggesting that the GM3 signal may be transduced via Akt.

Original languageEnglish
Pages (from-to)438-443
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume356
Issue number2
DOIs
Publication statusPublished - 2007 May 4

Fingerprint

G(M3) Ganglioside
Glucosylceramides
Experimental Melanomas
Phosphorylation
Small Interfering RNA
Tumor Necrosis Factor-alpha
Sialyltransferases
Cytidine Monophosphate
Galactosyltransferases
Uridine Diphosphate
Phosphatidylinositols
Blood
Phosphotransferases
Complementary DNA
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
1-Phosphatidylinositol 4-Kinase
Monocytes

Keywords

  • Akt
  • Ganglioside GM3
  • LY294,002
  • PI3K
  • TNFα
  • Wortmannin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Positive regulation of tumor necrosis factor-α by ganglioside GM3 through Akt in mouse melanoma B16 cells. / Wang, Pu; Wu, Peixing; Zhang, Jinghai; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya.

In: Biochemical and Biophysical Research Communications, Vol. 356, No. 2, 04.05.2007, p. 438-443.

Research output: Contribution to journalArticle

Wang, Pu ; Wu, Peixing ; Zhang, Jinghai ; Sato, Toshinori ; Yamagata, Sadako ; Yamagata, Tatsuya. / Positive regulation of tumor necrosis factor-α by ganglioside GM3 through Akt in mouse melanoma B16 cells. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 356, No. 2. pp. 438-443.
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