Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells
Backgrounds: High-altitude pulmonary edema (HAPE) is a life-threatening disease without effective drugs. Caffeine is a small molecule compound with antioxidant biological activity used to treat respiratory distress syndrome. However, it is unclear whether caffeine plays a role in alleviating HAPE.Me...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1155414/full |
| _version_ | 1797852971107614720 |
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| author | Liuyang Tian Liuyang Tian Liuyang Tian Zhilong Jia Zhilong Jia Yan Yan Qian Jia Qian Jia Wenjie Shi Saijia Cui Huining Chen Yang Han Yang Han Yang Han Xiaojing Zhao Xiaojing Zhao Kunlun He Kunlun He Kunlun He |
| author_facet | Liuyang Tian Liuyang Tian Liuyang Tian Zhilong Jia Zhilong Jia Yan Yan Qian Jia Qian Jia Wenjie Shi Saijia Cui Huining Chen Yang Han Yang Han Yang Han Xiaojing Zhao Xiaojing Zhao Kunlun He Kunlun He Kunlun He |
| author_sort | Liuyang Tian |
| collection | DOAJ |
| description | Backgrounds: High-altitude pulmonary edema (HAPE) is a life-threatening disease without effective drugs. Caffeine is a small molecule compound with antioxidant biological activity used to treat respiratory distress syndrome. However, it is unclear whether caffeine plays a role in alleviating HAPE.Methods: We combined a series of biological experiments and label-free quantitative proteomics analysis to detect the effect of caffeine on treating HAPE and explore its mechanism in vivo and in vitro.Results: Dry and wet weight ratio and HE staining of pulmonary tissues showed that the HAPE model was constructed successfully, and caffeine relieved pulmonary edema. The proteomic results of mice lungs indicated that regulating mitochondria might be the mechanism by which caffeine reduced HAPE. We found that caffeine blocked the reduction of ATP production and oxygen consumption rate, decreased ROS accumulation, and stabilized mitochondrial membrane potential to protect AT1 cells from oxidative stress damage under hypoxia. Caffeine promoted the PINK1/parkin-dependent mitophagy and enhanced mitochondrial fission to maintain the mitochondria quality control process.Conclusion: Low-dose of caffeine alleviated HAPE by promoting PINK1/parkin-dependent mitophagy and mitochondrial fission to control the mitochondria quality. Therefore, caffeine could be a potential treatment for HAPE. |
| first_indexed | 2024-04-09T19:41:52Z |
| format | Article |
| id | doaj.art-37c1e0e314c647b6a1ffd248910a3007 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T19:41:52Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-37c1e0e314c647b6a1ffd248910a30072023-04-04T04:23:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-04-011410.3389/fphar.2023.11554141155414Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cellsLiuyang Tian0Liuyang Tian1Liuyang Tian2Zhilong Jia3Zhilong Jia4Yan Yan5Qian Jia6Qian Jia7Wenjie Shi8Saijia Cui9Huining Chen10Yang Han11Yang Han12Yang Han13Xiaojing Zhao14Xiaojing Zhao15Kunlun He16Kunlun He17Kunlun He18School of Medicine, Nankai University, Tianjin, ChinaMedical Big Data Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaCenter for Artificial Intelligence in Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaTechnical Research Centre for Prevention and Control of Birth Defects, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaMedical Big Data Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaResearch Center for Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaMedical Big Data Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaNational Engineering Research Center for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaBackgrounds: High-altitude pulmonary edema (HAPE) is a life-threatening disease without effective drugs. Caffeine is a small molecule compound with antioxidant biological activity used to treat respiratory distress syndrome. However, it is unclear whether caffeine plays a role in alleviating HAPE.Methods: We combined a series of biological experiments and label-free quantitative proteomics analysis to detect the effect of caffeine on treating HAPE and explore its mechanism in vivo and in vitro.Results: Dry and wet weight ratio and HE staining of pulmonary tissues showed that the HAPE model was constructed successfully, and caffeine relieved pulmonary edema. The proteomic results of mice lungs indicated that regulating mitochondria might be the mechanism by which caffeine reduced HAPE. We found that caffeine blocked the reduction of ATP production and oxygen consumption rate, decreased ROS accumulation, and stabilized mitochondrial membrane potential to protect AT1 cells from oxidative stress damage under hypoxia. Caffeine promoted the PINK1/parkin-dependent mitophagy and enhanced mitochondrial fission to maintain the mitochondria quality control process.Conclusion: Low-dose of caffeine alleviated HAPE by promoting PINK1/parkin-dependent mitophagy and mitochondrial fission to control the mitochondria quality. Therefore, caffeine could be a potential treatment for HAPE.https://www.frontiersin.org/articles/10.3389/fphar.2023.1155414/fullcaffeinehigh altitude pulmonary edema (HAPE)mitochondrialmitochondrial quality controlproteomics |
| spellingShingle | Liuyang Tian Liuyang Tian Liuyang Tian Zhilong Jia Zhilong Jia Yan Yan Qian Jia Qian Jia Wenjie Shi Saijia Cui Huining Chen Yang Han Yang Han Yang Han Xiaojing Zhao Xiaojing Zhao Kunlun He Kunlun He Kunlun He Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells Frontiers in Pharmacology caffeine high altitude pulmonary edema (HAPE) mitochondrial mitochondrial quality control proteomics |
| title | Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells |
| title_full | Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells |
| title_fullStr | Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells |
| title_full_unstemmed | Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells |
| title_short | Low-dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in AT1 cells |
| title_sort | low dose of caffeine alleviates high altitude pulmonary edema via regulating mitochondrial quality control process in at1 cells |
| topic | caffeine high altitude pulmonary edema (HAPE) mitochondrial mitochondrial quality control proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1155414/full |
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