Zinc promotes cell proliferation via regulating metal-regulatory transcription factor 1 expression and transcriptional activity in pulmonary arterial hypertension.

Article

作者: Xie, Liangdi ; Lian, Guili ; Liu, Junping ; Xu, Changsheng ; Gao, Gufeng ; Wang, Huajun ; Luo, Li ; Gong, Jin ; Chen, Ai ; Chen, Weixiao

Metal responsive transcription factor 1 (MTF-1) is a zinc-dependent transcription factor involved in the development of pulmonary arterial hypertension (PAH), which is a life-threatening disease characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling. However, little is known about the role and regulatory signaling of MTF-1 in PAH. This study aimed to investigate the effect and mechanism of MTF-1 on the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Several techniques including intracellular-free zinc detected by fluorescent indicator-fluozinc-3-AM, western blot, luciferase reporter, and cell proliferation assay were conducted to perform a comprehensive analysis of MTF-1 in proliferation of PASMCs in PAH. Increased cytosolic zinc was shown in monocrotaline (MCT)-PASMCs and ZnSO₄-treated PASMCs, which led to overexpression and overactivation of MTF-1, followed by the up-regulation of placental growth factor (PlGF). Elevated MTF-1 and PlGF were observed in western blot, and high transcriptional activity of MTF-1 was confirmed by luciferase reporter in ZnSO₄-treated cells. Further investigation of cell proliferation revealed a favorable impact of zinc ions on PASMCs proliferation, with the deletion of Mtf-1/Plgf attenuating ZnSO₄-induced proliferation. Flow cytometry analysis showed that blockade of PKC signaling inhibited the cell cycle of MCT-PASMCs and ZnSO4-treated PASMCs. The Zinc/PKC/MTF-1/PlGF pathway is involved in the up-regulatory effect on the PASMCs proliferation in the process of PAH. This study provided novel insight into zinc homeostasis in the pathogenesis of PAHs, and the regulation of MTF-1 might be a potential target for therapeutic intervention in PAH.

2022-05-20·ChemSusChem2区 · 化学

Metal‐Thiolate Framework for Electrochemical and Photoelectrochemical Hydrogen Generation

2区 · 化学

Article

作者: Mukherjee, Manjistha ; Chatterjee, Sauvik ; Chongdar, Sayantan ; Bhaumik, Asim ; Shaymal, Sanjib ; Paul, Ankan ; Halder, Debabrata

AbstractHydrogen has evolved as the cleanest and most sustainable fuel, produced directly from naturally abundant water resources. Generation of hydrogen by electrochemical or photoelectrochemical splitting of water has been conceived as the most effective method for hydrogen production. Herein, a robust solid metal‐thiolate framework (MTF‐1) was obtained by hydrothermal crystallization of the reaction mixture consisting of 1,3,5‐triazine‐2,4,6‐trithioltrisodium salt and CuIIunder mild synthesis conditions. The material was thoroughly characterized and explored as efficient catalyst for electrochemical and photoelectrochemical hydrogen evolution reaction (HER) via water splitting reactions. MTF‐1 showed onset potential 0.045 VRHEand overpotentialη(@10 mA cm−2) at 0.096 VRHE. The electrochemical surface area of MTF‐1 was found to be 509 m2 g−1. The photo current density at pH 5.0 was found to be 0.487 mA cm−2at 0.6 VRHE. The feasibility of the reaction pathway was correlated from the density function theory study, which suggested the complete downhill energetics indicating spontaneous electrochemical hydrogen generation in the acidic medium.

2018-08-01·BioMetals3区 · 生物学

Bioinformatic analysis of the metal response element and zinc-dependent gene regulation via the metal response element-binding transcription factor 1 in Caco-2 cells

3区 · 生物学

Article

作者: Francis, Michael ; Grider, Arthur

The purpose of this study was to determine the correlation between the position or number of metal regulatory elements (MREs) near gene transcriptional or translational start sites, and the strength of metal response element-binding transcription factor 1 (MTF-1) regulation. A secondary analysis was performed in silico on published results measuring the effects of Zn and MTF-1 on transcriptional regulation of genes (n = 120) in the Caco-2 cell line. MRE sequence variations throughout the human genome were sorted using a position weight matrix. Three null hypotheses (H₀) were tested: (1) there is no correlation between the number of MREs and MTF-1 transcriptional strength, (2) there is no correlation between the distance of the MRE upstream from the transcriptional start site (TSS) and MTF-1 transcriptional strength, and (3) there is no correlation between the distance of the MRE downstream from the translational start site (TrSS) and MTF-1 transcriptional strength. Spearman correlation was used to test for significance (p < 0.05). From our results we rejected the first H₀; we observed a significant correlation between the total number of MRE sequences - 7Kbp upstream from the TSS, within the 5' untranslated region, and + 1Kbp downstream from the TrSS, versus the strength of MTF-1 regulation (r = 0.202; p = 0.027). The second and third H₀ were accepted. These results expand our understanding of the role of the MRE in Zn-dependent gene regulation. The data indicate that Zn influences the transcriptional control of gene expression beyond maintaining intracellular Zn homeostasis.

100 项与 MTF-001 相关的药物交易

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