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, Toshio

doi:10.1016/j.bbrc.2007.02.152

Cited by 13 publications

(29 citation statements)

References 28 publications

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“…In our previous work, GM3 administered to mouse melanoma B16 cells was shown to upregulate TNF-α mRNA through the PI3K-Akt pathway [15]. In order to confirm whether TNF-α protein production was enhanced by GM3 treatment of B16 cells, cells and culture medium were separately collected.…”

Section: Resultsmentioning

confidence: 99%

“…Phosphorylation of Akt (Ser 473 ) was determined under the same conditions as above. Phosphorylated Akt content was elevated 1.7 times in the presence of GM3 [15], suggesting the GM3 signal to be transduced through the Akt pathway (fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

“…An aliquot of the lysate was electrophoresed, blotted and subjected to Western blotting as detailed in the previous paper [15]. …”

Section: Methodsmentioning

confidence: 99%

“…Recently, we have shown GM3 to positively regulate TNF-α expression via a PI3K/Akt pathway in mouse melanoma B16 cells [15]. The GM3 signal was shown to be located upstream of Akt, but whether it is located upstream of PI3K remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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GM3 Signals Regulating TNF-Alpha Expression Are Mediated by Rictor and Arhgdib in Mouse Melanoma B16 Cells

Wang¹,

Yang²,

et al. 2007

Oncology

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Objective: We have previously shown GM3 to positively regulate TNF-α expression via a PI3K/Akt pathway in mouse melanoma B16 cells [Wang et al.: Biochem Biophys Res Commun 2007;356:438–443]. The GM3 signal was shown to be located upstream of Akt, but whether it is located upstream of PI3K and which molecule is the effector of PI3K remain to be clarified. Methods: We used inhibitors of PI3K and mTOR, and siRNA directed to Rictor, Raptor and Rho-GDP dissociation inhibitor β (Arhgdib). Results: PI3K inhibitors LY294002 and LY303511 were shown to suppress TNF-α expression that is stimulated by GM3 in B16 cells, suggesting that the GM3 signal is located upstream of the PI3K-Akt pathway. Rapamycin suppressed TNF-α expression, indicating mTOR to be involved in the pathway. Either siRNA Raptor or siRNA Rictor suppressed TNF-α expression, but the latter suppressed the effects of GM3 on TNF-α expression and Akt phosphorylation at Ser⁴⁷³, indicating the GM3 signal to be transduced via Rictor/mTOR and Akt (Ser⁴⁷³), leading to TNF-α stimulation. Finally, Arhgdib, the tumor suppressor gene whose expression is associated with GM3, was shown to be upstream of TNF-α. Conclusions: The GM3 signal is thus transduced in B16 cells through a PI3K, Rictor/mTOR, Akt, Arhgdib pathway, leading to stimulated expression ofTNF-α.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…An aliquot of the lysate was electrophoresed, blotted and subjected to Western blotting as detailed in the previous paper [15]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GM3 Signals Regulating TNF-Alpha Expression Are Mediated by Rictor and Arhgdib in Mouse Melanoma B16 Cells

Wang¹,

Yang²,

et al. 2007

Oncology

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“…Treatment of B16 cells with small interfering RNA (siRNA) targeted to Akt1/2 resulted in TNF α suppression, indicating that Akt plays an important role in regulation of TNF α expression. Suppression of Akt1/2 rendered cells insensitive to GM3, suggesting that the GM3 signal may be transduced via Akt (Wang et al, 2007a). 3.…”

Section: Gm3 Promotes Cell Motility Via Inducing Matrix Metalloproteimentioning

confidence: 99%

Changing the Nature of Melanoma Cells by Manipulation of Ganglioside Expression

Wang¹,

Yamagata²,

Yamagata³

2011

Breakthroughs in Melanoma Research

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Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB, AP‐1, and MAPKs signaling

Park

Kwak

et al. 2017

J of Cellular Biochemistry

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Gangliosides are known to specifically inhibit vascular leukocyte recruitment and consequent interaction with the injured endothelium, the basic inflammatory process. In this study, we have found that the production of nitric oxide (NO), a main regulator of inflammation, is suppressed by GM3 on murine macrophage RAW 264.7 cells, when induced by LPS. In addition, GM3 attenuated the increase in cyclooxyenase-2 (COX-2) protein and mRNA levels in lipopolysaccharide (LPS)-activated RAW 264.7 cells in a dose-dependent manner. Moreover, GM3 inhibited the expression and release of pro-inflammatory cytokines of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW 264.7 macrophages. At the intracellular level, GM3 inhibited LPS-induced nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein (AP)-1 in RAW 264.7 macrophages. We, therefore, investigated whether GM3 affects mitogen-activated protein kinase (MAPK) phosphorylation, a process known as the upstream signaling regulator. GM3 dramatically reduced the expression levels of the phosphorylated forms of ERK, JNK, and p38 in LPS-activated RAW 264.7 cells.Abbreviations: AP-1, activator protein-1; COX-2, cyclooxyenase-2; DMEM, Dulbecco's Modified Eagle Medium; ECL, enhanced chemiluminescence; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; GM3, monosialodihexosylganglioside; iNOS, inducible nitric oxide synthase; IL-1β, interleukin-1β; LPS, lipopolysaccharide; MAPKs, mitogen-activated protein kinases; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PGE2, prostaglandin E2; PGH2, prostaglandin H2; TBE, Tris-borate-EDTA; TLR, Toll-like receptors; TNF-α, tumor necrosis factor-α.

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

Cited by 13 publications

References 28 publications

GM3 Signals Regulating TNF-Alpha Expression Are Mediated by Rictor and Arhgdib in Mouse Melanoma B16 Cells

GM3 Signals Regulating TNF-Alpha Expression Are Mediated by Rictor and Arhgdib in Mouse Melanoma B16 Cells

Changing the Nature of Melanoma Cells by Manipulation of Ganglioside Expression

Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB, AP‐1, and MAPKs signaling

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