Cadmium stimulation of plasminogen activator inhibitor-1 release from human vascular endothelial cells in culture

Yamamoto, Chika; Kaji, Tatsuru; Sakamoto, Michiko; Kono, Hiroshi

doi:10.1016/0300-483x(93)90103-y

Cited by 50 publications

(24 citation statements)

References 25 publications

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“…20) Based on this result, we first confirmed whether or not the increased accumulation of PAI-1 actually results in a reduction of plasminogen activator activity in the conditioned medium using fibrin zymography. As shown in Fig.…”

Section: Resultsmentioning

confidence: 56%

“…18,19) In our previous study, it was shown that cadmium does not influence the secretion of t-PA but promotes that of PAI-1 in cultured human vascular endothelial cells. 20) However, it has been unclear whether or not the activity of either t-PA or u-PA is actually reduced by the excess accumulation of PAI-1 in the conditioned medium. In addition, it is also incompletely understood whether or not stimulation of the PAI-1 secretion by cadmium is a reflection of induction of the synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Induction of Plasminogen Activator Inhibitor Type 1 Synthesis by Cadmium in Human Vascular Endothelial Cells in Culture.

Yamamoto

Kaji

2002

JOURNAL OF HEALTH SCIENCE

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Cadmium is a unique heavy metal that stimulates the secretion of plasminogen activator inhibitor type 1 (PAI-1) from vascular endothelial cells. However, it has been incompletely understood whether cadmium stimulation of PAI-1 secretion actually results in a reduction of endothelial fibrinolytic activity and whether the stimulation results from an induction of endothelial PAI-1 synthesis. To address these questions, human umbilical vein endothelial cells were cultured with cadmium chloride in the presence or absence of actinomycin D, H-7 or HA1004. The activity of tissue type and urokinase type plasminogen activators (t-PA and u-PA, respectively) in the conditioned medium was analyzed by fibrin zymography and mRNAs coding t-PA, u-PA and PAI-1 were determined by quantitative reverse transcription-polymerase chain reaction. Results of the experiments indicate that cadmium reduces the activity of both t-PA and u-PA in vascular endothelial cells through induction of PAI-1 synthesis which is mediated by protein kinase C activation. Since the PAI-1 induction by cadmium was observed in neither human vascular smooth muscle cells nor human fibroblasts, it was suggested that vascular endothelial cells are a particular cell type of which PAI-1 synthesis is stimulated by cadmium.

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Section: Resultsmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Induction of Plasminogen Activator Inhibitor Type 1 Synthesis by Cadmium in Human Vascular Endothelial Cells in Culture.

Yamamoto

Kaji

2002

JOURNAL OF HEALTH SCIENCE

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“…However, one aspect of this process that has received only slight attention concerns the role of the vascular endothelial cells in the activation of Kupffer cells and the subsequent inflammatory response. Studies on vascular endothelial cells in culture have shown that treatment with micromolar-millimolar concentrations of Cd causes the cells to produce and/or release a variety of cytokines and proinflammatory molecules (Kaji, 2004;Mlynek and Skoczynska, 2005;Nelson et al, 1991;Yamamoto et al, 1993). However, it is not known whether these types of mediators are released by endothelial cells under the lower levels of exposure that would occur in vivo.…”

Section: Hepatotoxicitymentioning

confidence: 93%

The vascular endothelium as a target of cadmium toxicity

2006

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“…Because cadmium exposure is a risk factor for atherosclerosis (Houtman, 1993;Fagerberg et al, 2012), we previously studied the cytotoxicity of cadmium in vascular endothelial cells using a cell culture system. Our analyses showed that vascular endothelial cells are sensitive to cadmium cytotoxicity (Kaji et al, 1996); cadmium influences the synthesis of heparan sulfate proteoglycans (Ohkawara et al, 1997) and lowers fibrinolytic activity by promoting the synthesis and secretion of plasminogen activator inhibitor-1 (Yamamoto et al, 1993;Yamamoto and Kaji, 2002). Endothelial cells can be protected from cadmium cytotoxicity by zinc (Kaji et al, 1992;Mishima et al, 1997).…”

Section: Introductionmentioning

confidence: 92%

Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells

et al. 2016

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-Vascular endothelial cells are in direct contact with blood. Inorganic zinc is thought to be incapable of inducing metallothionein, which protects cells from heavy metal toxicity and oxidative stress, in vascular endothelial cells. Here, we aimed to further characterize the induction of metallothionein in vascular endothelial cells. Our results confirmed that inorganic zinc could not induce metallothionein in vascular endothelial cells. Moreover, ZnSO 4 could not activate both the metal response element (MRE) transcription factor 1 (MTF-1)/MRE and Nrf2/antioxidant response element (ARE) pathways and was incapable of inducing metallothionein. In addition, bis(L-cysteinato)zincate(II), a zinc complex that activates the MTF-1/MRE pathway, increased MRE promoter activity but failed to induce metallothionein, suggesting that vascular endothelial metallothionein was not induced only by activation of the MTF-1/MRE pathway. Further analysis of a library of zinc complexes showed that zinc(II) bis(diethyldithiocarbamate) activated the MTF-1/MRE pathway but not the Nrf2/ARE pathway, increased MT-1A, MT-1E, and MT-2A mRNA levels, and induced metallothionein proteins. These data indicated that zinc complexes may be excellent tools to analyze metallothionein induction in vascular endothelial cells.

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Cadmium stimulation of plasminogen activator inhibitor-1 release from human vascular endothelial cells in culture

Cited by 50 publications

References 25 publications

Induction of Plasminogen Activator Inhibitor Type 1 Synthesis by Cadmium in Human Vascular Endothelial Cells in Culture.

Induction of Plasminogen Activator Inhibitor Type 1 Synthesis by Cadmium in Human Vascular Endothelial Cells in Culture.

The vascular endothelium as a target of cadmium toxicity

Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells

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