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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Published in | Redox report : communications in free radical research Vol. 27; no. 1; pp. 270 - 278 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Taylor & Francis
31.12.2022
Taylor & Francis Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Supplemental data for this article can be accessed online at https://doi.org/10.1080/13510002.2022.2143114. Xijuan Wang and Shuai Lv contributed equally. |
ISSN: | 1351-0002 1743-2928 |
DOI: | 10.1080/13510002.2022.2143114 |