Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund's adjuvant-induced inflammatory pain mouse model.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-02-04 DOI:10.1038/s41420-025-02322-1

Ngoc Buu Tran, Sook-Jeong Lee

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Abstract

Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients' physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund's adjuvant (CFA)-induced intracellular Zn²⁺ activity in an MT3 knockout mouse model of inflammatory pain in the hind paw. The results demonstrated that increasing intracellular Zn²⁺ levels ameliorate deficits in motor behavior, as well as inflammation in the paw, spleen, and thymus. Furthermore, intracellular Zn²⁺ was crucial in regulating oxidative stress markers (glutathione, superoxide dismutase, catalase, and malondialdehyde) and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in MT3 knockout mice induced with CFA. This study highlights the critical role of MT3 in coordinating the intracellular interaction with Zn²⁺, which is vital for the immune systems's protective functions. These interactions are fundamental for maintaining metal ion homeostasis and regulating the synthesis of various biomolecules in the body.

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.