Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway
Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups:...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2022.2143114 |
| _version_ | 1828099302720798720 |
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| author | Xijuan Wang Shuai Lv Jianwei Sun Meihui Zhang Lei Zhang Yan Sun Ziyan Zhao Dandan Wang Xinjing Zhao Jiajie Zhang |
| author_facet | Xijuan Wang Shuai Lv Jianwei Sun Meihui Zhang Lei Zhang Yan Sun Ziyan Zhao Dandan Wang Xinjing Zhao Jiajie Zhang |
| author_sort | Xijuan Wang |
| collection | DOAJ |
| description | Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 μM caffeine), antagonist (5 μM ZM241385), agonist (5 μM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. A2AR may serve as a promising therapeutic target for BPD in prematurity. |
| first_indexed | 2024-04-11T08:13:57Z |
| format | Article |
| id | doaj.art-a943f4bf4d74483aa24524855f793725 |
| institution | Directory Open Access Journal |
| issn | 1351-0002 1743-2928 |
| language | English |
| last_indexed | 2024-04-11T08:13:57Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj.art-a943f4bf4d74483aa24524855f7937252022-12-22T04:35:14ZengTaylor & Francis GroupRedox Report1351-00021743-29282022-12-0127127027810.1080/13510002.2022.2143114Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathwayXijuan Wang0Shuai Lv1Jianwei Sun2Meihui Zhang3Lei Zhang4Yan Sun5Ziyan Zhao6Dandan Wang7Xinjing Zhao8Jiajie Zhang9Department of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaDepartment of Paediatrics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, People’s Republic of ChinaObjectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 μM caffeine), antagonist (5 μM ZM241385), agonist (5 μM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. A2AR may serve as a promising therapeutic target for BPD in prematurity.https://www.tandfonline.com/doi/10.1080/13510002.2022.2143114CaffeineapoptosisA2ARcAMPPKAROS |
| spellingShingle | Xijuan Wang Shuai Lv Jianwei Sun Meihui Zhang Lei Zhang Yan Sun Ziyan Zhao Dandan Wang Xinjing Zhao Jiajie Zhang Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway Redox Report Caffeine apoptosis A2AR cAMP PKA ROS |
| title | Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway |
| title_full | Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway |
| title_fullStr | Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway |
| title_full_unstemmed | Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway |
| title_short | Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway |
| title_sort | caffeine reduces oxidative stress to protect against hyperoxia induced lung injury via the adenosine a2a receptor camp pka src erk1 2 p38mapk pathway |
| topic | Caffeine apoptosis A2AR cAMP PKA ROS |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2022.2143114 |
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