Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen
Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324009898 |
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| author | Xiaoqian Ran Xi Yan Guanwei Ma Zhiyuan Liang Hongbin Zhuang Xiaoxiao Tang Xiaolu Chen Xueshan Cao Xukun Liu Yuhan Huang Yi Wang Xinglai Zhang Peng Luo Liming Shen |
| author_facet | Xiaoqian Ran Xi Yan Guanwei Ma Zhiyuan Liang Hongbin Zhuang Xiaoxiao Tang Xiaolu Chen Xueshan Cao Xukun Liu Yuhan Huang Yi Wang Xinglai Zhang Peng Luo Liming Shen |
| author_sort | Xiaoqian Ran |
| collection | DOAJ |
| description | Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury. In this study, a Sprague-Dawley (SD) rat model of As-poisoned was established, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen. After feeding the rats with As diet (50 mg/kg) for 90 days, the spleen tissue of the rats in the As-poisoned group was damaged, the level of As was significantly higher than that of the control group (P < 0.001), and the level of inflammatory cytokine interleukin-6 (IL-6) was decreased (P < 0.01). Proteomics and metabolomics results showed that a total of 134 differentially expressed proteins (DEPs) (P < 0.05 and fold change > 1.2) and 182 differentially expressed metabolites (DEMs) (VIP >1 and P < 0.05) were identified in the spleens of the As poisoned group compared to the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cell mediated cytotoxicity, and ribosomes. The major pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. The integrated analysis of these two omics suggested that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure. The results indicate that As exposure can cause spleen damage in rats. Through proteomic and metabolomic analysis, the key proteins and metabolites and their associated mechanisms were obtained, which provided a basis for further understanding of the molecular mechanism of spleen immune damage caused by As exposure. |
| format | Article |
| id | doaj-art-555f8146d67b409db8fe34d6e2f465ed |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-555f8146d67b409db8fe34d6e2f465ed2025-08-20T01:54:44ZengElsevierEcotoxicology and Environmental Safety0147-65132024-10-0128411691310.1016/j.ecoenv.2024.116913Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleenXiaoqian Ran0Xi Yan1Guanwei Ma2Zhiyuan Liang3Hongbin Zhuang4Xiaoxiao Tang5Xiaolu Chen6Xueshan Cao7Xukun Liu8Yuhan Huang9Yi Wang10Xinglai Zhang11Peng Luo12Liming Shen13School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaCollege of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR ChinaSchool of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University, Guiyang 561113, China; Guizhou Ecological Food Innovation Engineering Research Center, Guiyang 561113, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; Corresponding authors at: School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR China.School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR China; College of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, PR China; Corresponding authors at: School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, PR China.Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury. In this study, a Sprague-Dawley (SD) rat model of As-poisoned was established, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen. After feeding the rats with As diet (50 mg/kg) for 90 days, the spleen tissue of the rats in the As-poisoned group was damaged, the level of As was significantly higher than that of the control group (P < 0.001), and the level of inflammatory cytokine interleukin-6 (IL-6) was decreased (P < 0.01). Proteomics and metabolomics results showed that a total of 134 differentially expressed proteins (DEPs) (P < 0.05 and fold change > 1.2) and 182 differentially expressed metabolites (DEMs) (VIP >1 and P < 0.05) were identified in the spleens of the As poisoned group compared to the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cell mediated cytotoxicity, and ribosomes. The major pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. The integrated analysis of these two omics suggested that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure. The results indicate that As exposure can cause spleen damage in rats. Through proteomic and metabolomic analysis, the key proteins and metabolites and their associated mechanisms were obtained, which provided a basis for further understanding of the molecular mechanism of spleen immune damage caused by As exposure.http://www.sciencedirect.com/science/article/pii/S0147651324009898ArsenicIntegrative analysisMetabolomicsNaAsO2ProteomicsSpleen |
| spellingShingle | Xiaoqian Ran Xi Yan Guanwei Ma Zhiyuan Liang Hongbin Zhuang Xiaoxiao Tang Xiaolu Chen Xueshan Cao Xukun Liu Yuhan Huang Yi Wang Xinglai Zhang Peng Luo Liming Shen Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen Ecotoxicology and Environmental Safety Arsenic Integrative analysis Metabolomics NaAsO2 Proteomics Spleen |
| title | Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen |
| title_full | Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen |
| title_fullStr | Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen |
| title_full_unstemmed | Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen |
| title_short | Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen |
| title_sort | integration of proteomics and metabolomics analysis investigate mechanism of as induced immune injury in rat spleen |
| topic | Arsenic Integrative analysis Metabolomics NaAsO2 Proteomics Spleen |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324009898 |
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