Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2023-09-01 DOI:10.1016/j.fct.2023.113950

Quanwei Li , Qingwen Yang , Pan Guo , Yuanhong Feng , Shaofeng Wang , Jianying Guo , Zhaoxin Tang , Wenlan Yu , Jianzhao Liao

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引用次数: 1

Abstract

Zinc (Zn) is a critical microelement for physiological process, but excess exposure can cause testicular dysfunction. However, the underlying mechanism of Zn-induced ferroptosis via regulating mitophagy is unknown. In this study, a total of 60 male weaned pigs were randomly divided into three groups and the content of Zn were 75 mg/kg (control), 750 mg/kg (Zn–I), 1500 mg/kg (Zn-II). Meanwhile, testicular cells were treated with ZnSO₄ (0, 50 and 100 μM), and in combination of ZnSO₄ (100 μM) and ferrostation-1, ML-210, or 3-methyladenine for 24 h. Our results verified that Zn could cause ferroptosis and lipid peroxidation, which were characterized by down-regulating level of SLC7A11, GPX4, and ferritin, and up-regulating levels of MDA, CD71, TF, and HMGB1 by Western blot, immunohistochemistry, immunofluorescence, peroxidase assay, et.ac. The opposite effect was shown after treatment with ferrostation-1 or ML-210. Meanwhile, the mitophagy-related proteins (PINK, Parkin, ATG5, LC3-II/LC3-I) were significantly upregulated in vivo and in vitro. Most importantly, 3-methyladenine observably relieved ferroptosis under Zn treatment through inhibiting mitophagy. Collectively, we demonstrated that mitophagy contributes to Zn-induced ferroptosis in porcine testis cells, providing a new insight into Zn toxicology.

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有丝分裂有助于锌诱导的猪睾丸细胞铁下垂

锌(Zn)是生理过程中重要的微量元素，但过量暴露会导致睾丸功能障碍。然而，锌通过调节有丝分裂诱导铁下垂的潜在机制尚不清楚。试验选用60头断奶公猪，随机分为3组，饲粮锌含量分别为75 mg/kg(对照)、750 mg/kg (Zn- i)、1500 mg/kg (Zn- ii)。同时，用ZnSO4(0、50、100 μM)和ZnSO4 (100 μM)与铁离子-1、ML-210、3-甲基腺嘌呤联用处理睾丸细胞24 h。Western blot、免疫组织化学、免疫荧光、过氧化物酶等检测结果表明，Zn可引起铁细胞凋亡和脂质过氧化，表现为SLC7A11、GPX4、铁蛋白水平下调，MDA、CD71、TF、HMGB1水平上调。用铁-1或ML-210处理后显示相反的效果。同时，线粒体自噬相关蛋白(PINK、Parkin、ATG5、LC3-II/LC3-I)在体内和体外均显著上调。最重要的是，3-甲基腺嘌呤通过抑制线粒体自噬明显缓解锌处理下的铁下垂。总之，我们证明了线粒体自噬有助于锌诱导的猪睾丸细胞铁下垂，为锌毒理学提供了新的见解。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.