CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium
IntroductionCadmium (Cd) and polystyrene microplastics (PS-MPs), two ubiquitous environmental contaminants, produce unique synergistic toxicity when co-existing. Key unanswered questions include specific effects on liver function and potential mechanisms.MethodsIn this study, C57BL/6 mice and AML12...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1533188/full |
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| author | Zhixuan Chen Huayi Qu Jian Sun Tao Wang Yan Yuan Yan Yuan Yan Yuan Jianhong Gu Jianhong Gu Jianhong Gu Jianchun Bian Jianchun Bian Jianchun Bian Zongping Liu Zongping Liu Zongping Liu Hui Zou Hui Zou Hui Zou |
| author_facet | Zhixuan Chen Huayi Qu Jian Sun Tao Wang Yan Yuan Yan Yuan Yan Yuan Jianhong Gu Jianhong Gu Jianhong Gu Jianchun Bian Jianchun Bian Jianchun Bian Zongping Liu Zongping Liu Zongping Liu Hui Zou Hui Zou Hui Zou |
| author_sort | Zhixuan Chen |
| collection | DOAJ |
| description | IntroductionCadmium (Cd) and polystyrene microplastics (PS-MPs), two ubiquitous environmental contaminants, produce unique synergistic toxicity when co-existing. Key unanswered questions include specific effects on liver function and potential mechanisms.MethodsIn this study, C57BL/6 mice and AML12 cells were used to establish in vivo and in vitro models to elucidate the effects of combined exposure to PS-MPs and Cd on the liver and their mechanisms.ResultsThe results showed that the combined effects of PS-MPs and Cd caused significantly more liver damage than exposure alone. As observed by transmission electron microscopy (TEM), the number of autophagosomes was significantly increased in the PS-MPs and Cd co-treated group. In addition, autophagic flux was assayed by RFP-GFP-LC3, a reporter system expressing dual fluorescent proteins, which showed an overwhelming enhancement of autophagic flux damage by co-exposure to PS-MPs and Cd compared to exposure alone. To further investigate the involvement of carnitine palmitoyltransferase1(CPT1) in liver injury induced by co-exposure to Cd and PS-MPs, we co-exposed Baicalin, an activator of CPT1, with PS-MPs and Cd, and showed that activation of CPT1 alleviated the impairment of autophagic fluxes induced by co-exposure of Cd and PS-MPs and further alleviated the changes in lipid accumulation and associated protein levels.DiscussionIn conclusion, the concurrent exposure of PS-MPs and Cd resulted in the blockage of hepatic lipid accumulation and autophagic pathway and further aggravated the toxic damage to the liver. Activation of CPT1 could alleviate the PS-MPs and Cd-induced lipid accumulation and autophagy pathway blockage thus reducing liver injury. |
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| id | doaj-art-f6b587410e744f39ab649a0232a74194 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-f6b587410e744f39ab649a0232a741942025-01-06T06:58:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15331881533188CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmiumZhixuan Chen0Huayi Qu1Jian Sun2Tao Wang3Yan Yuan4Yan Yuan5Yan Yuan6Jianhong Gu7Jianhong Gu8Jianhong Gu9Jianchun Bian10Jianchun Bian11Jianchun Bian12Zongping Liu13Zongping Liu14Zongping Liu15Hui Zou16Hui Zou17Hui Zou18College of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaIntroductionCadmium (Cd) and polystyrene microplastics (PS-MPs), two ubiquitous environmental contaminants, produce unique synergistic toxicity when co-existing. Key unanswered questions include specific effects on liver function and potential mechanisms.MethodsIn this study, C57BL/6 mice and AML12 cells were used to establish in vivo and in vitro models to elucidate the effects of combined exposure to PS-MPs and Cd on the liver and their mechanisms.ResultsThe results showed that the combined effects of PS-MPs and Cd caused significantly more liver damage than exposure alone. As observed by transmission electron microscopy (TEM), the number of autophagosomes was significantly increased in the PS-MPs and Cd co-treated group. In addition, autophagic flux was assayed by RFP-GFP-LC3, a reporter system expressing dual fluorescent proteins, which showed an overwhelming enhancement of autophagic flux damage by co-exposure to PS-MPs and Cd compared to exposure alone. To further investigate the involvement of carnitine palmitoyltransferase1(CPT1) in liver injury induced by co-exposure to Cd and PS-MPs, we co-exposed Baicalin, an activator of CPT1, with PS-MPs and Cd, and showed that activation of CPT1 alleviated the impairment of autophagic fluxes induced by co-exposure of Cd and PS-MPs and further alleviated the changes in lipid accumulation and associated protein levels.DiscussionIn conclusion, the concurrent exposure of PS-MPs and Cd resulted in the blockage of hepatic lipid accumulation and autophagic pathway and further aggravated the toxic damage to the liver. Activation of CPT1 could alleviate the PS-MPs and Cd-induced lipid accumulation and autophagy pathway blockage thus reducing liver injury.https://www.frontiersin.org/articles/10.3389/fphar.2024.1533188/fullautophagycadmiumliverlipid metabolismpolystyrene microplastics |
| spellingShingle | Zhixuan Chen Huayi Qu Jian Sun Tao Wang Yan Yuan Yan Yuan Yan Yuan Jianhong Gu Jianhong Gu Jianhong Gu Jianchun Bian Jianchun Bian Jianchun Bian Zongping Liu Zongping Liu Zongping Liu Hui Zou Hui Zou Hui Zou CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium Frontiers in Pharmacology autophagy cadmium liver lipid metabolism polystyrene microplastics |
| title | CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium |
| title_full | CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium |
| title_fullStr | CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium |
| title_full_unstemmed | CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium |
| title_short | CPT1 deficiency blocks autophagic flux to promote lipid accumulation induced by co-exposure to polystyrene microplastic and cadmium |
| title_sort | cpt1 deficiency blocks autophagic flux to promote lipid accumulation induced by co exposure to polystyrene microplastic and cadmium |
| topic | autophagy cadmium liver lipid metabolism polystyrene microplastics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1533188/full |
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