Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells

Song, Naree; Kim, Seok Jo; Kwon, Haw Young; Son, Sung Wook; Kim, Kyoung Sook; Ahn, Hee Bae; Lee, Young Choon

doi:10.5483/bmbrep.2011.44.6.405

Cited by 13 publications

(21 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell viability assay was performed as described previously [7,8,9,10,11]. The amount of formazan produced was quantified by measuring the absorbance at 490 nm with an ELISA plate reader (Bio-Rad, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Recently we studied the transcriptional regulation mechanism of human sialyltransferase genes that are specifically expressed at high levels in cell lines treated with natural compounds [7,8,9,10,11]. In the current study, we investigated the effect of physcion isolated from the Polygonum multiflorum roots on the human sialyltransferase gene expression in SK-N-BE(2)-C human neuroblastoma cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells

Yoon

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

In this research, we firstly demonstrated that physcion, an anthraquinone derivative, specifically increased the expression of the human α2,8-sialyltransferase (hST8Sia VI) gene in SK-N-BE(2)-C human neuroblastoma cells. To establish the mechanism responsible for the up-regulation of hST8Sia VI gene expression in physcion-treated SK-N-BE(2)-C cells, the putative promoter region of the hST8Sia VI gene was functionally characterized. Promoter analysis with serially truncated fragments of the 5′-flanking region showed that the region between −320 and −240 is crucial for physcion-induced transcription of hST8Sia VI in SK-N-BE(2)-C cells. Putative binding sites for transcription factors Pax-5 and NF-Y are located at this region. The Pax-5 binding site at −262 to −256 was essential for the expression of the hST8Sia VI gene by physcion in SK-N-BE(2)-C cells. Moreover, the transcription of hST8Sia VI induced by physcion in SK-N-BE(2)-C cells was inhibited by extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, but not c-Jun N-terminal kinase (JNK) inhibitor SP600125. These results suggest that physcion upregulates hST8Sia VI gene expression via ERK and p38 MAPK pathways in SK-N-BE(2)-C cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells

Yoon

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…1-4). Valproic acid is a known up-regulator of GM3 synthase gene (16), and it is also known as an inhibitor of histone deacetylase (14,15). Therefore, it is possible that valproic acid may control the expression of other genes.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to GM3, valproic acid, which is known as an anticonvulsant and mood-stabilizing drug and a histone deacetylase inhibitor (13)(14)(15), has been shown to up-regulate ST3GAL5 gene expression (16). In a recent clinical trial, the potential application of valproic acid in treating cancers, especially high grade gliomas, was examined, and it was observed that valproic acid had some therapeutic effect on glioma (17).…”

Section: Glycosphingolipid Gm3mentioning

confidence: 99%

“…They also observed that valproic acid inhibited secretion of VEGF from glioma cells that might have resulted from an indirect effect of valproic acid on angiogenesis (24). Valproic acid is a known histone deacetylase inhibitor (14,15), and expression of several genes (including ST3GAL5) has been shown to be altered by valproic acid treatment (14,16). Many mechanisms have been proposed to explain the antitumor effect of valproic acid (25,26).…”

Section: Gm3 Induction Suppresses Cancer Cell Growthmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth

Kawashima

Nishimiya

Takahata

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Glycosphingolipid GM3, a known suppressor of epidermal growth factor receptor (EGFR) phosphorylation, inhibits cell proliferation. Valproic acid, conversely, is known as an up-regulator of GM3 synthase gene (ST3GAL5). To test the possibility that valproic acid could inhibit EGFR phosphorylation by increasing the level of GM3 in cells, we treated A431 epidermoid carcinoma cells with valproic acid and found that valproic acid treatment caused an about 6-fold increase in the GM3 level but only a marginal increase in the GM2 level in these cells and that the observed increase in GM3 level was valproic acid dose-dependent. Consistent with this observation, valproic acid treatment induced GM3 synthase gene expression by about 8-fold. Furthermore, phosphorylation of EGFR was reduced, and cell proliferation was inhibited following valproic acid treatment. Consistent with these results, transient expression of GM3 synthase gene in A431 cells also increased cellular level of GM3, reduced phosphorylation of EGFR, and inhibited cell proliferation. Treatment with l-phenyl-2-decanoylamino-3-morpholino-l-propanol, an inhibitor of glucosylceramide synthesis, decreased the cellular level of GM3 and reduced the inhibitory effects of valproic acid on EGFR phosphorylation and cell proliferation. These results suggested that induction of GM3 synthesis was enough to inhibit proliferation of cancer cells by suppressing EGFR activity. Valproic acid treatment similarly increased the GM3 level and reduced phosphorylation of EGFR in U87MG glioma cells and inhibited their proliferation. These results suggested that up-regulators of GM3 synthase gene, such as valproic acid, are potential suppressors of cancer cell proliferation. Glycosphingolipid GM32 is one of the well studied gangliosides. GM3 is synthesized by transferring sialic acid to lactosylceramide, a step catalyzed by a sialyltransferase known as GM3 synthase, which is encoded by the ST3GAL5 gene (1). GM3 is a common precursor for the synthesis of all ganglio series glycolipids, and it is widely expressed in many organs.GM3 is known as a modulator of growth factor receptors and insulin receptor (2-4). Particularly, modulation of epidermal growth factor receptor (EGFR) by GM3 has been well studied. For modulation of receptor activity, it is essential that GM3 binds to its receptor. There are two possible ways GM3 can bind to a receptor: 1) binding via sialic acid of GM3 and basic amino acid residues of the receptor as has been found in the case of insulin receptor and GM3 (5) and 2) binding via carbohydrateto-carbohydrate interaction as has been observed between GM3 and N-glycans of EGFR (6, 7). The binding of GM3 to these receptors prevented receptor dimerization and inhibited phosphorylation of receptors (8).Several previous studies have shown that GM3 level in cells changes on transformation (9, 10). For example, transformation of fibroblast cells by v-Jun greatly reduced GM3 levels in transformed cells, and increased synthesis of GM3 reversed the oncogenic properties of the cel...

show abstract

Regulatory mechanism for the human glioblastoma cell-specific expression of the human GD1c/GT1a/GQ1b synthase (hST8Sia V) gene

An,

Lee,

Kim

et al. 2023

Glycoconj J

Self Cite

View full text Add to dashboard Cite

In this study we observed that human GD1c/GT1a/GQ1b synthase (hST8Sia V) is particularly expressed in human glioblastoma cells. To address the mechanism regulating human glioblastoma-speci c gene expression of the hST8Sia V, after the transcription start site (TSS) was identi ed by the 5'-rapid ampli cation of cDNA end with total RNA from human glioblastoma U87MG cells, the 5'-anking region (2.5 kb) of the hST8Sia V gene was isolated and its promoter activity was examined. By luciferase reporter assay, this 5'-anking region revealed strong promoter activity in only U-87MG cells, but not in other tissue-derived cancer cells. 5'-deletion mutant analysis showed that the region from -1140 to -494 is crucial for transcription of the hST8Sia V gene in U87MG cells. This region contains the activator protein-1 (AP-1) binding site, the main target of the c-Jun N-terminal kinase (JNK) downstream. The AP-1 binding site at -1043/-1037 was proved to be indispensable for the hST8Sia V gene-speci c expression in U87MG cells by site-directed mutagenesis. Moreover, the transcriptional activation of hST8Sia V gene in U87MG cells was strongly inhibited by a speci c JNK inhibitor, SP600125. These results suggest that the hST8Sia V gene-speci c expression in U87MG cells is controlled by JNK/AP-1 signaling pathway.

show abstract

Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells

Abstract: The present study demonstrated that valproic acid (VPA) transcriptionally regulates human GM3 synthase (hST3Gal V), which catalyzes ganglioside GM3 biosynthesis in ARPE-19 human retinal pigment epithelial cells.

Cited by 13 publications

References 16 publications

Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells

Upregulation of Human ST8Sia VI (α2,8-Sialyltransferase) Gene Expression by Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells

Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth

Regulatory mechanism for the human glioblastoma cell-specific expression of the human GD1c/GT1a/GQ1b synthase (hST8Sia V) gene

Contact Info

Product

Resources

About