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金属硫蛋白在人类病理生理学中的新作用:综述

Emerging Roles of Metallothioneins in Human Pathophysiology: A Review.

作者信息

Mohammed Ousman, Tufa Abdisa, Gizaw Solomon Tebeje

机构信息

Department of Medical Biochemistry, School of Medicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia.

Department of Medical Laboratory Sciences, College of Medicine and Health Sciences Wollo University Dessie Ethiopia.

出版信息

Health Sci Rep. 2025 Sep 22;8(9):e71279. doi: 10.1002/hsr2.71279. eCollection 2025 Sep.

DOI:10.1002/hsr2.71279
PMID:40994777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12453973/
Abstract

BACKGROUND

Metallothioneins (MTs) are small molecular-weight proteins that either bind or release essential transition metals, depending on a specific cell situation. There are 4 major isoforms of MTs (1-4), of which MT1/2 is found in every cell in the body.

AIM

To provide a comprehensive discussion on the role of metallothionein in human pathophysiology.

METHODS

This review was conducted using a variety of search engines, including Google Scholar, PubMed Central, Scopus, Web of Science, and others.

RESULTS

The antioxidant property of MT is enhanced based on the availability of zinc. MTs reduce Pro-inflammatory cytokine production and shift the Th17/Treg balance, ultimately alleviating inflammatory diseases. In neurodegenerative diseases, MTs interact with protein aggregates and modulate their formation and toxicity. The MT's molecular processes in neurodegenerative illnesses include metal ion control, antioxidant activity, and anti-inflammatory actions. In cancer, MT acts as a tumor suppressor in the early stages and promotes tumor progression in the later stages. Only a few MT isoform-targeting approaches have been approved for use as therapeutic drugs.

CONCLUSION

Metallothioneins play vital roles in controlling oxidative stress, immunity, metal homeostasis and protein aggregate for many diseases. Their dual roles as defenders in inflammation and neurodegeneration, and as suppressors and facilitators in cancer, highlight the complex nature of their biological role.

摘要

背景

金属硫蛋白(MTs)是小分子蛋白质,可根据特定细胞情况结合或释放必需的过渡金属。MTs有4种主要亚型(1 - 4),其中MT1/2存在于人体的每个细胞中。

目的

全面讨论金属硫蛋白在人类病理生理学中的作用。

方法

本综述使用了多种搜索引擎进行,包括谷歌学术、PubMed Central、Scopus、科学网等。

结果

基于锌的可用性,MT的抗氧化特性增强。MTs减少促炎细胞因子的产生并改变Th17/Treg平衡,最终减轻炎症性疾病。在神经退行性疾病中,MTs与蛋白质聚集体相互作用并调节其形成和毒性。MT在神经退行性疾病中的分子过程包括金属离子控制、抗氧化活性和抗炎作用。在癌症中,MT在早期阶段起肿瘤抑制作用,而在后期促进肿瘤进展。只有少数针对MT亚型的方法已被批准用作治疗药物。

结论

金属硫蛋白在控制氧化应激、免疫、金属稳态和蛋白质聚集方面对许多疾病起着至关重要的作用。它们在炎症和神经退行性变中作为防御者,以及在癌症中作为抑制者和促进者的双重作用,凸显了其生物学作用的复杂性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/119bee805e79/HSR2-8-e71279-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/60345990ae90/HSR2-8-e71279-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/f9b4e9d68857/HSR2-8-e71279-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/119bee805e79/HSR2-8-e71279-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/60345990ae90/HSR2-8-e71279-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/f9b4e9d68857/HSR2-8-e71279-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac59/12453973/119bee805e79/HSR2-8-e71279-g003.jpg

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本文引用的文献

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Front Pharmacol. 2025 Jan 31;16:1478013. doi: 10.3389/fphar.2025.1478013. eCollection 2025.
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Computer-aided analysis reveals metallothionein-positive cancer-associated fibroblasts promote angiogenesis in gastric adenocarcinoma.计算机辅助分析显示,金属硫蛋白阳性的癌症相关成纤维细胞促进胃腺癌血管生成。
Discov Oncol. 2024 Dec 5;15(1):751. doi: 10.1007/s12672-024-01614-9.
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MT1G promotes iron autophagy and inhibits the function of gastric cancer cell lines by intervening in GPX4/SQSTM1.
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