Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2
Fine particulate matter (PM2.5) airborne pollution increases the risk of respiratory and cardiovascular diseases. Although metformin is a well-known antidiabetic drug, it also confers protection against a series of diseases through the activation of AMP-activated protein kinase (AMPK). However, whet...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231719309784 |
| _version_ | 1811286495737151488 |
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| author | Junling Gao Juntao Yuan Qiao'e Wang Tong Lei Xiyue Shen Bingqing Cui Fang Zhang Wenjun Ding Zhongbing Lu |
| author_facet | Junling Gao Juntao Yuan Qiao'e Wang Tong Lei Xiyue Shen Bingqing Cui Fang Zhang Wenjun Ding Zhongbing Lu |
| author_sort | Junling Gao |
| collection | DOAJ |
| description | Fine particulate matter (PM2.5) airborne pollution increases the risk of respiratory and cardiovascular diseases. Although metformin is a well-known antidiabetic drug, it also confers protection against a series of diseases through the activation of AMP-activated protein kinase (AMPK). However, whether metformin affects PM2.5-induced adverse health effects has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2−/− mice to PM2.5 every other day via intratracheal instillation for 4 weeks. After PM2.5 exposure, the AMPKα2−/− mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKα2−/− mice. In the PM2.5-exposed mice, metformin treatment resulted in reduced systemic and pulmonary inflammation, preserved left ventricular ejection fraction, suppressed induction of pulmonary and myocardial fibrosis and oxidative stress, and increased levels of mitochondrial antioxidant enzymes. Moreover, pretreatment with metformin significantly attenuated PM2.5-induced cell death and oxidative stress in control and AMPKα2-depleted BEAS-2B and H9C2 cells, and was associated with preserved expression of mitochondrial antioxidant enzymes. These data support the notion that metformin protects against PM2.5-induced adverse health effects through a pathway that appears independent of AMPKα2. Our findings suggest that metformin may also be a novel drug for therapies that treat air pollution associated disease. Keywords: Metformin, AMPKα2, PM2.5, Lung injury, Cardiac dysfunction |
| first_indexed | 2024-04-13T03:00:57Z |
| format | Article |
| id | doaj.art-6fc9d5dd80c848e49f1f27bdb8d57aaf |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T03:00:57Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-6fc9d5dd80c848e49f1f27bdb8d57aaf2022-12-22T03:05:26ZengElsevierRedox Biology2213-23172020-01-0128Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2Junling Gao0Juntao Yuan1Qiao'e Wang2Tong Lei3Xiyue Shen4Bingqing Cui5Fang Zhang6Wenjun Ding7Zhongbing Lu8College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaKey Laboratory of Cosmetic, China National Light Industry, Beijing Technology and Business University, Beijing, 100048, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author.College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. College of Life Sciences, University of Chinese Academy of Sciences, NO 19A, Yuquanlu, Shijingshan District, Beijing, 100049, China.Fine particulate matter (PM2.5) airborne pollution increases the risk of respiratory and cardiovascular diseases. Although metformin is a well-known antidiabetic drug, it also confers protection against a series of diseases through the activation of AMP-activated protein kinase (AMPK). However, whether metformin affects PM2.5-induced adverse health effects has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2−/− mice to PM2.5 every other day via intratracheal instillation for 4 weeks. After PM2.5 exposure, the AMPKα2−/− mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKα2−/− mice. In the PM2.5-exposed mice, metformin treatment resulted in reduced systemic and pulmonary inflammation, preserved left ventricular ejection fraction, suppressed induction of pulmonary and myocardial fibrosis and oxidative stress, and increased levels of mitochondrial antioxidant enzymes. Moreover, pretreatment with metformin significantly attenuated PM2.5-induced cell death and oxidative stress in control and AMPKα2-depleted BEAS-2B and H9C2 cells, and was associated with preserved expression of mitochondrial antioxidant enzymes. These data support the notion that metformin protects against PM2.5-induced adverse health effects through a pathway that appears independent of AMPKα2. Our findings suggest that metformin may also be a novel drug for therapies that treat air pollution associated disease. Keywords: Metformin, AMPKα2, PM2.5, Lung injury, Cardiac dysfunctionhttp://www.sciencedirect.com/science/article/pii/S2213231719309784 |
| spellingShingle | Junling Gao Juntao Yuan Qiao'e Wang Tong Lei Xiyue Shen Bingqing Cui Fang Zhang Wenjun Ding Zhongbing Lu Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 Redox Biology |
| title | Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 |
| title_full | Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 |
| title_fullStr | Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 |
| title_full_unstemmed | Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 |
| title_short | Metformin protects against PM2.5-induced lung injury and cardiac dysfunction independent of AMP-activated protein kinase α2 |
| title_sort | metformin protects against pm2 5 induced lung injury and cardiac dysfunction independent of amp activated protein kinase α2 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231719309784 |
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