Possible mechanisms underlying transcriptional induction of metallothionein isoforms by tris(pentafluorophenyl)stibane, tris(pentafluorophenyl)arsane, and tris(pentafluorophenyl)phosphane in cultured bovine aortic endothelial cells

Fujie, Tomoya; Takenaka, Fukuta; Yoshida, Eiko; Yasuike, Shuji; Fujiwara, Yasuyuki; Shinkai, Yasuhiro; Kumagai, Yoshito; Yamamoto, Chika; Kaji, Toshiyuki

doi:10.2131/jts.44.327

Cited by 14 publications

(9 citation statements)

References 19 publications

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“…Deletion of Nrf2 suppressed the ZnO-NP-induced increase in metallothionein-1 but increased the background level of metallothionein-2 expression. Metallothionein-1 and -2 are known to be regulated by metal response element (MRE), but recent studies show transcriptional induction of metallothionein-1 thorough Nrf2 /ARE pathway [51–53], which might partly explain the suppression of ZnO-NP-induced increase in metallothionein-1. Metallothioneins are cysteine-rich and heavy metal-binding proteins known to contribute to a wide range of protective cellular responses.…”

Section: Discussionmentioning

confidence: 99%

Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

Sehsah

Ichihara

et al. 2019

Part Fibre Toxicol

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BackgroundZinc oxide nanoparticles (ZnO-NPs) are widely used in many industrial sectors and previous studies have reported that exposure of the lungs to ZnO-NPs induces both acute and/or chronic pulmonary inflammation, but the exact mechanism underlying such response remains elusive. This study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by exposure to ZnO-NPs using Nrf2 null (Nrf2−/−) mice.MethodsTwenty-four male Nrf2−/− mice and thirty male wild type C57BL/6 J mice were divided into three groups of eight and ten each respectively, and exposed once to ZnO-NPs at 0, 10, 30 μg/mouse by pharyngeal aspiration. At 14 days after the exposure to ZnO-NPs, bronchoalveolar lavage fluid (BALF) and lungs were collected to quantify protein level and the number of inflammatory cells. The mRNA levels of Nrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured.ResultsExposure to ZnO-NPs dose-dependently increased the number of total cells, macrophages, lymphocytes and eosinophils in BALF both in Nrf2−/− mice and wild type mice, but the magnitude of increase was significantly higher in Nrf2−/− mice than wild type mice. The number of neutrophils in BALF increased in Nrf2−/− mice, being accompanied by marginal trend of increase in mRNA expression of MIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level of Nrf2-dependent antioxidant enzymes both in Nrf2−/− mice and wild type mice.ConclusionPharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally induced Nrf2-dependent antioxidant enzymes. The results suggest that Nrf2 play a role in negative regulation on ZnO-NP exposure-induced neutrophil migration, but does not demonstrate that the regulation is through suppression of oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

Sehsah

Ichihara

et al. 2019

Part Fibre Toxicol

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“…Cu10 has been found to induce endothelial metallothionein, a cytoprotective protein. Subsequent studies using this copper complex have revealed that metallothionein induction is mediated by different intracellular signaling pathways for different metallothionein isoforms [20][21][22]. Proteoglycans synthesized by vascular endothelial cells play important roles in regulating the growth factor/cytokine activity [23] and blood-coagulation [24].…”

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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“…Nobuhiro Kajihara et al found that low glucose conditions exacerbated mtROS production through activation of fatty acid oxidation in bovine aortic endothelial cells [18]. Other researchers have also used cattle as their own experimental models [19][20][21][22][23][24]. We used the GSE75240 dataset to show that gut microbes can change the expression of proteins or genes in the blood.…”

Section: Discussionmentioning

confidence: 99%

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis

Liu

Yuan

et al. 2020

Med Sci Monit

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Background: Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. Material/Methods: The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. Results: We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. Conclusions: Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.

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Possible mechanisms underlying transcriptional induction of metallothionein isoforms by tris(pentafluorophenyl)stibane, tris(pentafluorophenyl)arsane, and tris(pentafluorophenyl)phosphane in cultured bovine aortic endothelial cells

Cited by 14 publications

References 19 publications

Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles

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

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis

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