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维生素C通过靶向Nrf2减少铁死亡来抑制鳞片脱落病病毒的感染性。

Vitamin C Inhibits Scale Drop Disease Virus Infectivity by Targeting Nrf2 to Reduce Ferroptosis.

作者信息

Chen Jiaming, Fu Yuting, Weng Shaoping, He Jianguo, Dong Chuanfu

机构信息

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

Institute of Aquatic Economic Animals, Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Sun Yat-sen University, Guangzhou 510275, China.

出版信息

Antioxidants (Basel). 2025 May 10;14(5):576. doi: 10.3390/antiox14050576.

DOI:10.3390/antiox14050576
PMID:40427458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12108497/
Abstract

Scale drop disease virus (SDDV) poses an escalating threat to global aquaculture, prompting an urgent need for research. Our study found that SDDV infection upregulates genes related to iron, oxidative stress, and lipid metabolism, causing iron overload, reactive oxygen species (ROS) accumulation, and ultimately ferroptosis. Among the tested antioxidants, vitamin C (VC) demonstrated the most potent inhibitory effect in mandarin fish, reducing SDDV-induced mortality by 37.5%. qPCR and IFA results showed that VC effectively suppressed SDDV infection; decreased ROS, lipid peroxidation (LPO), and iron levels; and enhanced glutathione peroxidase 4 (GPX4) expression in infected cells. Mechanistically, VC's inhibitory effect was reversed by the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML-385, indicating an Nrf2-dependent pathway. VC promoted Nrf2 nuclear translocation and activated downstream antioxidant genes. Moreover, VC modulated inflammation by regulating pro- and anti-inflammatory factors. These findings suggest VC as a promising therapeutic for SDDV infection.

摘要

鳞片脱落病病毒(SDDV)对全球水产养殖业构成了日益严重的威胁,这促使人们迫切需要开展相关研究。我们的研究发现,SDDV感染会上调与铁、氧化应激和脂质代谢相关的基因,导致铁过载、活性氧(ROS)积累,并最终引发铁死亡。在所测试的抗氧化剂中,维生素C(VC)对鳜鱼表现出最有效的抑制作用,将SDDV诱导的死亡率降低了37.5%。定量聚合酶链反应(qPCR)和免疫荧光分析(IFA)结果表明,VC能有效抑制SDDV感染;降低ROS、脂质过氧化(LPO)和铁水平;并增强感染细胞中谷胱甘肽过氧化物酶4(GPX4)的表达。从机制上讲,核因子红细胞2相关因子2(Nrf2)抑制剂ML-385可逆转VC的抑制作用,表明这是一条依赖Nrf2的途径。VC促进Nrf2核转位并激活下游抗氧化基因。此外,VC通过调节促炎和抗炎因子来调节炎症。这些发现表明,VC有望成为治疗SDDV感染的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/e589590bbf7b/antioxidants-14-00576-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/f0c9db321db0/antioxidants-14-00576-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/9b6f6ecc9ae7/antioxidants-14-00576-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/e589590bbf7b/antioxidants-14-00576-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/f0c9db321db0/antioxidants-14-00576-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/c11027a50021/antioxidants-14-00576-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/8b79b98c5cf6/antioxidants-14-00576-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/47c6e76cd017/antioxidants-14-00576-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/9b6f6ecc9ae7/antioxidants-14-00576-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff0c/12108497/e589590bbf7b/antioxidants-14-00576-g007.jpg

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本文引用的文献

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Scale drop disease virus (SDDV) triggers ferroptosis both in mandarin fish (Siniperca chuatsi) and MFF-1 cells to facilitate virus infection via linking to transferrin receptor 1 (TfR1).鳞片脱落病病毒(SDDV)通过与转铁蛋白受体1(TfR1)结合,在鳜鱼(Siniperca chuatsi)和MFF-1细胞中引发铁死亡,以促进病毒感染。
Fish Shellfish Immunol. 2025 Aug;163:110416. doi: 10.1016/j.fsi.2025.110416. Epub 2025 May 13.
2
Potential of NRF2 Inhibitors-Retinoic Acid, K67, and ML-385-In Overcoming Doxorubicin Resistance in Promyelocytic Leukemia Cells.NRF2 抑制剂-维甲酸、K67 和 ML-385 克服早幼粒细胞白血病细胞多柔比星耐药的潜力。
Int J Mol Sci. 2024 Sep 24;25(19):10257. doi: 10.3390/ijms251910257.
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Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.
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