Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: Cell density-dependent effects prevented by sulfation

Yamamoto, Chika; Morita, Yuki; Yamaguchi, Shinya; Hayashi, Toshimitsu; Kaji, Tatsuru

doi:10.1016/j.lfs.2005.05.071

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…The structure of Cu10 is shown in Figure 1a. Because the response of vascular endothelial cells to exogenous factors is often cell density-dependent [32][33][34][35][36], both dense and sparse cultures of the cells were used in this experiment. CSE protein expression was not altered by Cu10 in dense (Figure 1b (Figure 1d, lower panels) cultures.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells

Fujie

Takahashi

et al. 2020

IJMS

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As toxic substances can enter the circulating blood and cross endothelial monolayers to reach parenchymal cells in organs, vascular endothelial cells are an important target compartment for such substances. Reactive sulfur species protect cells against oxidative stress and toxic substances, including heavy metals. Reactive sulfur species are produced by enzymes, such as cystathionine γ-lyase (CSE), cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and cysteinyl-tRNA synthetase. However, little is known about the regulatory mechanisms underlying the expression of these enzymes in vascular endothelial cells. Bio-organometallics is a research field that analyzes biological systems using organic-inorganic hybrid molecules (organometallic compounds and metal coordinating compounds) as molecular probes. In the present study, we analyzed intracellular signaling pathways that mediate the expression of reactive sulfur species-producing enzymes in cultured bovine aortic endothelial cells, using copper diethyldithiocarbamate (Cu10). Cu10 selectively upregulated CSE gene expression in vascular endothelial cells independent of cell density. This transcriptional induction of endothelial CSE required both the diethyldithiocarbamate scaffold and the coordinated copper ion. Additionally, the present study revealed that ERK1/2, p38 MAPK, and hypoxia-inducible factor (HIF)-1α/HIF-1β pathways mediate transcriptional induction of endothelial CSE by Cu10. The transcription factors NF-κB, Sp1, and ATF4 were suggested to act in constitutive CSE expression, although the possibility that they are involved in the CSE induction by Cu10 cannot be excluded. The present study used a copper complex as a molecular probe to reveal that the transcription of CSE is regulated by multiple pathways in vascular endothelial cells, including ERK1/2, p38 MAPK, and HIF-1α/HIF-1β. Bio-organometallics appears to be an effective strategy for analyzing the functions of intracellular signaling pathways in vascular endothelial cells.

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Section: Introductionmentioning

confidence: 99%

Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells

Fujie

Takahashi

et al. 2020

IJMS

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The Biological Effects of Depolymerized Sodium Spirulan and Sulfated Colominic Acid on Vascular Cells are Beneficial in Preventing Atherosclerosis

Yamamoto

Fujiwara

Kaji

2006

JOURNAL OF HEALTH SCIENCE

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Atherosclerosis is a vascular lesion that is a common health problem in advanced countries. Functional damage of the vascular endothelial cells, vascular smooth muscle cell hyperplasia, and procoagulant/antifibrinolytic state of blood are generally observed in the lesion. Since polysaccharides such as heparin modulate vascular cell behavior through interaction with cytokines/growth factors, we hypothesized that polysaccharides from natural sources may possess beneficial biological activities that prevent atherosclerosis. Changes in cultured aortic endothelial and smooth muscle cells were investigated after treatment with the polysaccharides sodium spirulan (Na-SP) -a sulfated polysaccharide obtained from a hot water extract of the blue-green alga Spirulina platensis -and colominic acid (CA)-prepared as a homopolymer of N-acetylneuraminic acid produced by Escherichia coli K1. The experiments suggest that depolymerized Na-SP and sulfated CA can function as precursors of the agents that prevent atherosclerosis. In particular, both the chemically modified polysaccharides significantly inhibit the proliferation of the arterial smooth muscle cells without exhibiting any toxic effects on the integrity of the vascular endothelial cell layers. The results also indicate that chemical modifications, for example, depolymerization of Na-SP and sulfation of CA, can control the biological effects of these polysaccharides on vascular cells.

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Sialic Acid as a Target for the Development of Novel Antiangiogenic Strategies

et al. 2018

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Sialic acid is associated with glycoproteins and gangliosides of eukaryotic cells. It regulates various molecular interactions, being implicated in inflammation and cancer, where its expression is regulated by sialyltransferases and sialidases. Angiogenesis, the formation of new capillaries, takes place during inflammation and cancer, and represents the outcome of several interactions occurring at the endothelial surface among angiogenic growth factors, inhibitors, receptors, gangliosides and cell-adhesion molecules. Here, we elaborate on the evidences that many structures involved in angiogenesis are sialylated and that their interactions depend on sialic acid with implications in angiogenesis itself, inflammation and cancer. We also discuss the possibility to exploit sialic acid as a target for the development of novel antiangiogenic drugs.

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Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: Cell density-dependent effects prevented by sulfation

Cited by 3 publications

References 39 publications

Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells

Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells

The Biological Effects of Depolymerized Sodium Spirulan and Sulfated Colominic Acid on Vascular Cells are Beneficial in Preventing Atherosclerosis

Sialic Acid as a Target for the Development of Novel Antiangiogenic Strategies

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