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Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12 Cells Exposed to Paraquat
Previous studies evaluated the adenosine receptor antagonists alone to determine their effects on oxidative stress, but little is known about adenosine’s protective efficacy when oxidative injury occurs in vivo. Adenosine is a crucial signaling molecule recognized by four distinct G-protein-coupled...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005745/ https://www.ncbi.nlm.nih.gov/pubmed/35431696 http://dx.doi.org/10.1177/15593258221093411 |
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author | Shang, Liangcheng Huang, Yaobiao Xie, Xin Ye, Sudan Chen, Chun |
author_facet | Shang, Liangcheng Huang, Yaobiao Xie, Xin Ye, Sudan Chen, Chun |
author_sort | Shang, Liangcheng |
collection | PubMed |
description | Previous studies evaluated the adenosine receptor antagonists alone to determine their effects on oxidative stress, but little is known about adenosine’s protective efficacy when oxidative injury occurs in vivo. Adenosine is a crucial signaling molecule recognized by four distinct G-protein-coupled receptors (GPCRs) (i.e., A1R, A2AR, A2BR, and A3R) and protects cells against pathological conditions. The present study was performed to evaluate the role of antagonist modulation in the setting of paraquat toxicity with adenosine pretreatment. First, PC12 cells were exposed to paraquat (850 μM) and adenosine (30 μM) to develop an in vitro model for the antagonist effect assay. Second, we found that the A1R antagonist DPCPX enhanced the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Moreover, the A2AR antagonist ZM241385 decreased the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Our findings indicate that adenosine protection requires a dual blockade of A1R and activation of A2AR to work at its full potential, and the A2B and A3 adenosine receptor antagonists increased paraquat-induced oxidative damage. This represents a novel pharmacological strategy based on A1/A2A interactions and can assist in clarifying the role played by AR antagonists in the treatment of neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-9005745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-90057452022-04-14 Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12 Cells Exposed to Paraquat Shang, Liangcheng Huang, Yaobiao Xie, Xin Ye, Sudan Chen, Chun Dose Response Original Article Previous studies evaluated the adenosine receptor antagonists alone to determine their effects on oxidative stress, but little is known about adenosine’s protective efficacy when oxidative injury occurs in vivo. Adenosine is a crucial signaling molecule recognized by four distinct G-protein-coupled receptors (GPCRs) (i.e., A1R, A2AR, A2BR, and A3R) and protects cells against pathological conditions. The present study was performed to evaluate the role of antagonist modulation in the setting of paraquat toxicity with adenosine pretreatment. First, PC12 cells were exposed to paraquat (850 μM) and adenosine (30 μM) to develop an in vitro model for the antagonist effect assay. Second, we found that the A1R antagonist DPCPX enhanced the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Moreover, the A2AR antagonist ZM241385 decreased the viability of paraquat-induced PC12 cells that underwent adenosine pretreatment. Our findings indicate that adenosine protection requires a dual blockade of A1R and activation of A2AR to work at its full potential, and the A2B and A3 adenosine receptor antagonists increased paraquat-induced oxidative damage. This represents a novel pharmacological strategy based on A1/A2A interactions and can assist in clarifying the role played by AR antagonists in the treatment of neurodegenerative diseases. SAGE Publications 2022-04-09 /pmc/articles/PMC9005745/ /pubmed/35431696 http://dx.doi.org/10.1177/15593258221093411 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Shang, Liangcheng Huang, Yaobiao Xie, Xin Ye, Sudan Chen, Chun Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12 Cells Exposed to Paraquat |
title | Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12
Cells Exposed to Paraquat |
title_full | Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12
Cells Exposed to Paraquat |
title_fullStr | Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12
Cells Exposed to Paraquat |
title_full_unstemmed | Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12
Cells Exposed to Paraquat |
title_short | Effect of Adenosine Receptor Antagonists on Adenosine-Pretreated PC12
Cells Exposed to Paraquat |
title_sort | effect of adenosine receptor antagonists on adenosine-pretreated pc12
cells exposed to paraquat |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005745/ https://www.ncbi.nlm.nih.gov/pubmed/35431696 http://dx.doi.org/10.1177/15593258221093411 |
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