Administration of protopine prevents mitophagy and acute lung injury in sepsis
Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an al...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1104185/full |
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| author | Zhong Xiao Zhong Xiao Zhong Xiao Juan Long Juan Long Juan Long Jie Zhang Jie Zhang Jie Zhang Zhimin Qiu Zhimin Qiu Zhimin Qiu Chen Zhang Chen Zhang Chen Zhang Hongbing Liu Hongbing Liu Hongbing Liu Xinyong Liu Xinyong Liu Xinyong Liu Kang Wang Kang Wang Kang Wang Yahui Tang Yahui Tang Yahui Tang Longwang Chen Longwang Chen Longwang Chen Zhongqiu Lu Zhongqiu Lu Zhongqiu Lu Guangju Zhao Guangju Zhao Guangju Zhao |
| author_facet | Zhong Xiao Zhong Xiao Zhong Xiao Juan Long Juan Long Juan Long Jie Zhang Jie Zhang Jie Zhang Zhimin Qiu Zhimin Qiu Zhimin Qiu Chen Zhang Chen Zhang Chen Zhang Hongbing Liu Hongbing Liu Hongbing Liu Xinyong Liu Xinyong Liu Xinyong Liu Kang Wang Kang Wang Kang Wang Yahui Tang Yahui Tang Yahui Tang Longwang Chen Longwang Chen Longwang Chen Zhongqiu Lu Zhongqiu Lu Zhongqiu Lu Guangju Zhao Guangju Zhao Guangju Zhao |
| author_sort | Zhong Xiao |
| collection | DOAJ |
| description | Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy.Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS).Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1β, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments.Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis. |
| first_indexed | 2024-03-13T06:45:50Z |
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| id | doaj.art-a1a113c3de484d7db1d71e7b26dac015 |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T06:45:50Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-a1a113c3de484d7db1d71e7b26dac0152023-06-08T06:20:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.11041851104185Administration of protopine prevents mitophagy and acute lung injury in sepsisZhong Xiao0Zhong Xiao1Zhong Xiao2Juan Long3Juan Long4Juan Long5Jie Zhang6Jie Zhang7Jie Zhang8Zhimin Qiu9Zhimin Qiu10Zhimin Qiu11Chen Zhang12Chen Zhang13Chen Zhang14Hongbing Liu15Hongbing Liu16Hongbing Liu17Xinyong Liu18Xinyong Liu19Xinyong Liu20Kang Wang21Kang Wang22Kang Wang23Yahui Tang24Yahui Tang25Yahui Tang26Longwang Chen27Longwang Chen28Longwang Chen29Zhongqiu Lu30Zhongqiu Lu31Zhongqiu Lu32Guangju Zhao33Guangju Zhao34Guangju Zhao35Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaEmergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, ChinaThe Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, ChinaIntroduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy.Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS).Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1β, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments.Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis.https://www.frontiersin.org/articles/10.3389/fphar.2023.1104185/fullsepsisacute lung injury/ALIprotopine/PTPinflammationmitophagy |
| spellingShingle | Zhong Xiao Zhong Xiao Zhong Xiao Juan Long Juan Long Juan Long Jie Zhang Jie Zhang Jie Zhang Zhimin Qiu Zhimin Qiu Zhimin Qiu Chen Zhang Chen Zhang Chen Zhang Hongbing Liu Hongbing Liu Hongbing Liu Xinyong Liu Xinyong Liu Xinyong Liu Kang Wang Kang Wang Kang Wang Yahui Tang Yahui Tang Yahui Tang Longwang Chen Longwang Chen Longwang Chen Zhongqiu Lu Zhongqiu Lu Zhongqiu Lu Guangju Zhao Guangju Zhao Guangju Zhao Administration of protopine prevents mitophagy and acute lung injury in sepsis Frontiers in Pharmacology sepsis acute lung injury/ALI protopine/PTP inflammation mitophagy |
| title | Administration of protopine prevents mitophagy and acute lung injury in sepsis |
| title_full | Administration of protopine prevents mitophagy and acute lung injury in sepsis |
| title_fullStr | Administration of protopine prevents mitophagy and acute lung injury in sepsis |
| title_full_unstemmed | Administration of protopine prevents mitophagy and acute lung injury in sepsis |
| title_short | Administration of protopine prevents mitophagy and acute lung injury in sepsis |
| title_sort | administration of protopine prevents mitophagy and acute lung injury in sepsis |
| topic | sepsis acute lung injury/ALI protopine/PTP inflammation mitophagy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1104185/full |
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