CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway
Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has been implicated in the pathogenesis of liver diseases. This study investigates the role of circRNA_1156 in neodymium nitrate (Nd(NO<sub>3</sub>)<sub>3</sub>)-induced hepatocyte ferroptosis. Our in v...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| author | Ning Wang Jing Leng Jing Xu Kelei Qian Zhiqing Zheng Gonghua Tao Ping Xiao Xinyu Hong |
| author_facet | Ning Wang Jing Leng Jing Xu Kelei Qian Zhiqing Zheng Gonghua Tao Ping Xiao Xinyu Hong |
| author_sort | Ning Wang |
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| description | Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has been implicated in the pathogenesis of liver diseases. This study investigates the role of circRNA_1156 in neodymium nitrate (Nd(NO<sub>3</sub>)<sub>3</sub>)-induced hepatocyte ferroptosis. Our in vitro experiments revealed that exposure to Nd(NO<sub>3</sub>)<sub>3</sub> (1.2 µM) significantly reduced the viability of AML12 hepatocytes (<i>p</i> < 0.01), increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) (<i>p</i> < 0.001), and depleted glutathione (GSH) (<i>p</i> < 0.001). However, overexpression of circRNA_1156 effectively reversed these effects and suppressed the expression of ACSL4 and PKCβII (<i>p</i> < 0.01). In our in vivo experiments, chronic exposure to Nd(NO<sub>3</sub>)<sub>3</sub> (7–55 mg/kg for 180 days) induced hepatic iron deposition, mitochondrial damage, and activation of the ACSL4/PKCβII pathway (<i>p</i> < 0.01). These adverse effects were significantly ameliorated by circRNA_1156 overexpression (<i>p</i> < 0.05). Our findings identify circRNA_1156 as a novel inhibitor of Nd(NO<sub>3</sub>)<sub>3</sub>-induced ferroptosis via downregulation of the ACSL4/PKCβII pathway, providing valuable therapeutic insights for hepatotoxicity caused by rare earth element compounds. |
| format | Article |
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| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-e2b71a4fe064486aab2a5e586ab82b2b2025-08-20T03:32:26ZengMDPI AGAntioxidants2076-39212025-06-0114670010.3390/antiox14060700CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling PathwayNing Wang0Jing Leng1Jing Xu2Kelei Qian3Zhiqing Zheng4Gonghua Tao5Ping Xiao6Xinyu Hong7Institute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaInstitute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, ChinaFerroptosis, a form of regulated cell death driven by lipid peroxidation, has been implicated in the pathogenesis of liver diseases. This study investigates the role of circRNA_1156 in neodymium nitrate (Nd(NO<sub>3</sub>)<sub>3</sub>)-induced hepatocyte ferroptosis. Our in vitro experiments revealed that exposure to Nd(NO<sub>3</sub>)<sub>3</sub> (1.2 µM) significantly reduced the viability of AML12 hepatocytes (<i>p</i> < 0.01), increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) (<i>p</i> < 0.001), and depleted glutathione (GSH) (<i>p</i> < 0.001). However, overexpression of circRNA_1156 effectively reversed these effects and suppressed the expression of ACSL4 and PKCβII (<i>p</i> < 0.01). In our in vivo experiments, chronic exposure to Nd(NO<sub>3</sub>)<sub>3</sub> (7–55 mg/kg for 180 days) induced hepatic iron deposition, mitochondrial damage, and activation of the ACSL4/PKCβII pathway (<i>p</i> < 0.01). These adverse effects were significantly ameliorated by circRNA_1156 overexpression (<i>p</i> < 0.05). Our findings identify circRNA_1156 as a novel inhibitor of Nd(NO<sub>3</sub>)<sub>3</sub>-induced ferroptosis via downregulation of the ACSL4/PKCβII pathway, providing valuable therapeutic insights for hepatotoxicity caused by rare earth element compounds.https://www.mdpi.com/2076-3921/14/6/700circRNA_1156neodymium nitrateferroptosisACSL4/PKCβII pathwayhepatocyte injury |
| spellingShingle | Ning Wang Jing Leng Jing Xu Kelei Qian Zhiqing Zheng Gonghua Tao Ping Xiao Xinyu Hong CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway Antioxidants circRNA_1156 neodymium nitrate ferroptosis ACSL4/PKCβII pathway hepatocyte injury |
| title | CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway |
| title_full | CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway |
| title_fullStr | CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway |
| title_full_unstemmed | CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway |
| title_short | CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway |
| title_sort | circrna 1156 attenuates neodymium nitrate induced hepatocyte ferroptosis by inhibiting the acsl4 pkcβii signaling pathway |
| topic | circRNA_1156 neodymium nitrate ferroptosis ACSL4/PKCβII pathway hepatocyte injury |
| url | https://www.mdpi.com/2076-3921/14/6/700 |
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