The mechanism of lycopene alleviating cadmium-inhibited glucose uptake ability of epithelioma papulosum cyprini cells: miR-375, oxidative stress , and actin cytoskeleton dysfunction

文献类型： 外文期刊

第一作者： Liu, Yuhao

作者： Liu, Yuhao;Qiu, Minna;Hao, Zhiyu;Liu, Yuhang;Chang, Minghang;Sun, Wei;Teng, Xiaohua;Wang, Shaochi;Wang, Xinquan;Liu, Xiumei

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关键词： Cadmium; Lycopene; Glucose uptake ability; miR-375; Reactive oxygen species

期刊名称：JOURNAL OF ENVIRONMENTAL MANAGEMENT （ 影响因子：8.4； 五年影响因子：8.6 ）

ISSN： 0301-4797

年卷期： 2025 年 380 卷

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收录情况： SCI

摘要： Cadmium (Cd) poses a threat to fish and human health. Carp is the most widely farmed fish, and it is necessary to study the mechanism of Cd toxicity and effective mitigation methods for Cd poisoning in carps. We previously found that Cd up-regulated miR-375 in common carp spleens, and that IRS1, a factor involved in glucose (GLU) uptake, was a potential target gene of miR-375. However, whether Cd can decrease GLU uptake ability in fish remains unknown. Oxidative stress (OS) and actin cytoskeleton dysfunction (ACD) can take part in the mechanisms of GLU uptake ability reduction. Lycopene (Lyc) is a natural plant antioxidant, and epithelioma papulosum cyprini (EPC) cells are a model cell to study carps. Therefore, we conducted experiments with Cd or/and Lyc treatments to investigate the mechanisms of Lyc alleviating Cd-cytotoxicity on EPC cells from the perspectives of miR-375, OS, ACD, and GLU uptake ability. We found that Lyc mitigated Cd-caused miR-375 increase, OS, ACD, and GLU uptake ability reduction. Moreover, miR-375 overexpression/knockdown experiments demonstrated that miR-375 mediated OS, ACD, and GLU uptake ability reduction and targeted regulated IRS1PI3K-AKT. Furthermore, NAC intervention experiment demonstrated that ROS mediated ACD and the reduction of GLU uptake via ROS/IRS1-PI3K-AKT. Taken together, Lyc alleviated Cd-decreased GLU uptake ability via miR375-ROS/IRS1-PI3K-AKT and miR-375/IRS1-PI3K-AKT pathways in EPC cells. Our findings highlighted significant role of miR-375 in Cd-induced toxicity and elucidated the mechanism by which Lyc alleviated Cd-induced toxicity. Our study can provide new information and new targets for resisting environmental pollutant stress in animals.

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