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芳香烃受体(AhR)在弹性蛋白衍生肽(VGVAPG)作用机制中的作用及其对神经甾体生成的影响。

Involvement of the aryl hydrocarbon receptor (AhR) in the mechanism of action of elastin-derived peptide (VGVAPG) and its impact on neurosteroidogenesis.

机构信息

Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.

Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.

出版信息

Neurochem Int. 2023 Dec;171:105615. doi: 10.1016/j.neuint.2023.105615. Epub 2023 Sep 27.

DOI:10.1016/j.neuint.2023.105615
PMID:37769996
Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor from the family of basic helix-loop-helix transcription factors. Several studies have indicated an important role of AhR signaling pathways in senescence, aging, and neurodegenerative diseases. During aging, elastin is degraded and elastin-derived peptides (EDPs) are formed. EDPs have been detected in human blood, serum, and cerebrospinal fluid. Literature data suggest a role of EDPs in the development of neurodegenerative diseases. However, the impact of EDPs on the AhR signaling pathway has never been investigated. Therefore, the aim of our paper was to study the role of AhR in the mechanism of action of the VGVAPG peptide (one of the EDPs) in mouse primary astrocytes in vitro. Our experiments have shown that AhR plays an important role in the EDP mechanism of action in a model of mouse primary astrocytes. Moreover, due to the involvement of Sirt3, Pparγ, AhR, Glb1, Nf-κb1, Ece1, Ide, and Nepr genes and the production and release of neurosteroids, VGVAPG can accelerate the development of neurodegenerative diseases in which the proper metabolism of astrocytes is crucial. Furthermore, our studies have proved that AhR is likely involved in the co-control of the Sirt1, Glb1, Nf-κb1, Ece1, and Nepr expression in astrocytes.

摘要

芳香烃受体 (AhR) 是碱性螺旋-环-螺旋转录因子家族中的配体激活转录因子。多项研究表明,AhR 信号通路在衰老、老化和神经退行性疾病中起着重要作用。在衰老过程中,弹性蛋白被降解,形成弹性蛋白衍生肽 (EDP)。EDP 已在人血液、血清和脑脊液中检测到。文献资料表明 EDP 在神经退行性疾病的发展中起作用。然而,EDP 对 AhR 信号通路的影响从未被研究过。因此,我们的论文旨在研究 AhR 在体外小鼠原代星形胶质细胞中 VGVAPG 肽(EDP 之一)作用机制中的作用。我们的实验表明,AhR 在体外小鼠原代星形胶质细胞的 EDP 作用机制中起重要作用。此外,由于 Sirt3、Pparγ、AhR、Glb1、Nf-κb1、Ece1、Ide 和 Nepr 基因的参与以及神经甾体的产生和释放,VGVAPG 可加速神经退行性疾病的发展,其中星形胶质细胞的适当代谢至关重要。此外,我们的研究证明 AhR 可能参与了星形胶质细胞中 Sirt1、Glb1、Nf-κb1、Ece1 和 Nepr 表达的共同调控。

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