Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells
| Autor: | Yoshito Kumagai, Takato Hara, Tomoya Fujie, Toshiyuki Kaji, Akane Takahashi, Hiroshi Naka, Asuka Soyama, Hideyo Takahashi, Musubu Takahashi, Kosho Makino, Chika Yamamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mitogen-activated protein kinase medicine.disease_cause lcsh:Chemistry 0302 clinical medicine Gene expression lcsh:QH301-705.5 Cells Cultured Spectroscopy biology Chemistry General Medicine Computer Science Applications Cell biology Endothelial stem cell 030220 oncology & carcinogenesis endothelial cell Ditiocarb MAP Kinase Signaling System Sulfurtransferase copper diethyldithiocarbamate Article Gene Expression Regulation Enzymologic Catalysis Inorganic Chemistry 03 medical and health sciences Downregulation and upregulation medicine Animals Physical and Theoretical Chemistry Molecular Biology Transcription factor cystathionine γ-lyase Aryl Hydrocarbon Receptor Nuclear Translocator Organic Chemistry ATF4 Cystathionine gamma-Lyase Endothelial Cells Hypoxia-Inducible Factor 1 alpha Subunit Cystathionine beta synthase 030104 developmental biology hypoxia-inducible factor-1 lcsh:Biology (General) lcsh:QD1-999 bio-organometallics biology.protein Cattle Endothelium Vascular Copper Sulfur Oxidative stress |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6053, p 6053 (2020) International Journal of Molecular Sciences Volume 21 Issue 17 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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 &gamma lyase (CSE), cystathionine &beta 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)-1&alpha /HIF-1&beta pathways mediate transcriptional induction of endothelial CSE by Cu10. The transcription factors NF-&kappa B, 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-1&alpha Bio-organometallics appears to be an effective strategy for analyzing the functions of intracellular signaling pathways in vascular endothelial cells. |
| Databáze: | OpenAIRE |
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