Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation
The brain barrier is an important structure for metal ion homeostasis. According to studies, lead (Pb) exposure disrupts the transportation of copper (Cu) through the brain barrier, which may cause impairment of the nervous system; however, the specific mechanism is unknown. The previous studies sug...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323003652 |
| _version_ | 1797840562053709824 |
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| author | Yang Liu Zai-Hua Zhao Tao Wang Jin-Yu Yao Wen-Qing Wei Li-Hong Su Shuang-Shuang Tan Zi-Xuan Liu Han Song Jing-Yuan Chen Wei Zheng Wen-Jing Luo Gang Zheng |
| author_facet | Yang Liu Zai-Hua Zhao Tao Wang Jin-Yu Yao Wen-Qing Wei Li-Hong Su Shuang-Shuang Tan Zi-Xuan Liu Han Song Jing-Yuan Chen Wei Zheng Wen-Jing Luo Gang Zheng |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | The brain barrier is an important structure for metal ion homeostasis. According to studies, lead (Pb) exposure disrupts the transportation of copper (Cu) through the brain barrier, which may cause impairment of the nervous system; however, the specific mechanism is unknown. The previous studies suggested the X-linked inhibitor of apoptosis (XIAP) is a sensor for cellular Cu level which mediate the degradation of the MURR1 domain-containing 1 (COMMD1) protein. XIAP/COMMD1 axis was thought to be an important regulator in Cu metabolism maintenance. In this study, the role of XIAP-regulated COMMD1 protein degradation in Pb-induced Cu disorders in brain barrier cells was investigated. Pb exposure significantly increased Cu levels in both cell types, according to atomic absorption technology testing. Western blotting and reverse transcription PCR (RT-PCR) showed that COMMD1 protein levels were significantly increased, whereas XIAP, ATP7A, and ATP7B protein levels were significantly decreased. However, there were no significant effects at the messenger RNA (mRNA) level (XIAP, ATP7A, and ATP7B). Pb-induced Cu accumulation and ATP7B expression were reduced when COMMD1 was knocked down by transient small interfering RNA (siRNA) transfection. In addition, transient plasmid transfection of XIAP before Pb exposure reduced Pb-induced Cu accumulation, increased COMMD1 protein levels, and decreased ATP7B levels. In conclusion, Pb exposure can reduce XIAP protein expression, increase COMMD1 protein levels, and specifically decrease ATP7B protein levels, resulting in Cu accumulation in brain barrier cells. |
| first_indexed | 2024-04-09T16:17:22Z |
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| id | doaj.art-be4eea3df78147878ec1ed18f50478f4 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-09T16:17:22Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-be4eea3df78147878ec1ed18f50478f42023-04-24T04:37:06ZengElsevierEcotoxicology and Environmental Safety0147-65132023-05-01256114861Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradationYang Liu0Zai-Hua Zhao1Tao Wang2Jin-Yu Yao3Wen-Qing Wei4Li-Hong Su5Shuang-Shuang Tan6Zi-Xuan Liu7Han Song8Jing-Yuan Chen9Wei Zheng10Wen-Jing Luo11Gang Zheng12Department of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, China; Department of Neurology, Nanjing Meishan Hospital, Nanjing 210000, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Health Service, PLA General Hospital, Beijing 100853, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaSchool of Health Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Occupational and Environmental Health and the Ministry-of-Education’s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, China; Corresponding author.The brain barrier is an important structure for metal ion homeostasis. According to studies, lead (Pb) exposure disrupts the transportation of copper (Cu) through the brain barrier, which may cause impairment of the nervous system; however, the specific mechanism is unknown. The previous studies suggested the X-linked inhibitor of apoptosis (XIAP) is a sensor for cellular Cu level which mediate the degradation of the MURR1 domain-containing 1 (COMMD1) protein. XIAP/COMMD1 axis was thought to be an important regulator in Cu metabolism maintenance. In this study, the role of XIAP-regulated COMMD1 protein degradation in Pb-induced Cu disorders in brain barrier cells was investigated. Pb exposure significantly increased Cu levels in both cell types, according to atomic absorption technology testing. Western blotting and reverse transcription PCR (RT-PCR) showed that COMMD1 protein levels were significantly increased, whereas XIAP, ATP7A, and ATP7B protein levels were significantly decreased. However, there were no significant effects at the messenger RNA (mRNA) level (XIAP, ATP7A, and ATP7B). Pb-induced Cu accumulation and ATP7B expression were reduced when COMMD1 was knocked down by transient small interfering RNA (siRNA) transfection. In addition, transient plasmid transfection of XIAP before Pb exposure reduced Pb-induced Cu accumulation, increased COMMD1 protein levels, and decreased ATP7B levels. In conclusion, Pb exposure can reduce XIAP protein expression, increase COMMD1 protein levels, and specifically decrease ATP7B protein levels, resulting in Cu accumulation in brain barrier cells.http://www.sciencedirect.com/science/article/pii/S0147651323003652BBBBCBCOMMD1ATP7BXIAP |
| spellingShingle | Yang Liu Zai-Hua Zhao Tao Wang Jin-Yu Yao Wen-Qing Wei Li-Hong Su Shuang-Shuang Tan Zi-Xuan Liu Han Song Jing-Yuan Chen Wei Zheng Wen-Jing Luo Gang Zheng Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation Ecotoxicology and Environmental Safety BBB BCB COMMD1 ATP7B XIAP |
| title | Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation |
| title_full | Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation |
| title_fullStr | Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation |
| title_full_unstemmed | Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation |
| title_short | Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation |
| title_sort | lead exposure disturbs atp7b mediated copper export from brain barrier cells by inhibiting xiap regulated commd1 protein degradation |
| topic | BBB BCB COMMD1 ATP7B XIAP |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323003652 |
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