Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke
Background: The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS). Methods: Sixty Sprague Dawley rats were r...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Journal of Intensive Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667100X2400094X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841560075379933184 |
|---|---|
| author | Ran Meng Zhengzhong Sun Ruxue Chi Yan Gu Yuxiang Zhang Jiaxing Wang |
| author_facet | Ran Meng Zhengzhong Sun Ruxue Chi Yan Gu Yuxiang Zhang Jiaxing Wang |
| author_sort | Ran Meng |
| collection | DOAJ |
| description | Background: The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS). Methods: Sixty Sprague Dawley rats were randomly divided into control (CON), control + Parkin overexpression (CON + Parkin), EHS, and EHS + Parkin overexpression (EHS + Parkin) groups. Parkin was overexpressed by injecting an adeno-associated virus carrying the Parkin gene into the tail vein, and a rat model of EHS was established. Pathological changes in the lung tissue were analyzed using microcomputed tomography (micro-CT), and the lung coefficient and pulmonary capillary permeability were measured. Enzyme-linked immunosorbent assay were used to determine the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α, and reactive oxygen species. The morphology of mitochondria in type Ⅱ epithelial cells of lung tissue was observed using transmission electron microscopy; and the apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, mitofusin-2 (MFN2), phosphatase and tensin homolog (PTEN), PTEN-L, p62, and the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by Western blotting, and the ratio of LC3II/LC3I was calculated. Results: Compared with the EHS group, the survival rate of rats in the EHS + Parkin group was significantly higher. Their lung coefficient and pulmonary vascular permeability decreased and the pathological changes were significantly alleviated (P <0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased (P <0.05), and the degree of mitochondrial swelling in pulmonary type II epithelial cells was alleviated. The apoptosis of lung tissue was alleviated, the colocalization of Pink1 and Parkin, LC3 and Tom20 was enhanced, and the ratio of LC3-II/LC3-I increased. The expression of Pink1, MFN2, PTEN-L, and p62 decreased, whereas the expression of PTEN was not significantly different from that in the EHS group (P >0.05). Conclusion: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying ALI in rats with EHS, and activation of Parkin overexpression-mediated mitophagy can alleviate ALI caused by EHS. |
| format | Article |
| id | doaj-art-ee78222e285549d9be586bdbbb17cf4d |
| institution | Kabale University |
| issn | 2667-100X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Intensive Medicine |
| spelling | doaj-art-ee78222e285549d9be586bdbbb17cf4d2025-01-05T04:28:47ZengElsevierJournal of Intensive Medicine2667-100X2025-01-01518999Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstrokeRan Meng0Zhengzhong Sun1Ruxue Chi2Yan Gu3Yuxiang Zhang4Jiaxing Wang5Graduate School of Hebei North University, Zhangjiakou, Hebei, China; Department of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaGraduate School of Hebei North University, Zhangjiakou, Hebei, China; Department of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaGraduate School of Hebei North University, Zhangjiakou, Hebei, China; Department of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China; Corresponding author: Jiaxing Wang, Department of Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing 10091, China.Background: The roles of the Pink1/Parkin pathway and mitophagy in lung injury during heat stroke remain unclear. In this study, we investigated the role of Pink1/Parkin-mediated mitophagy in acute lung injury (ALI) in rats with exertional heat stroke (EHS). Methods: Sixty Sprague Dawley rats were randomly divided into control (CON), control + Parkin overexpression (CON + Parkin), EHS, and EHS + Parkin overexpression (EHS + Parkin) groups. Parkin was overexpressed by injecting an adeno-associated virus carrying the Parkin gene into the tail vein, and a rat model of EHS was established. Pathological changes in the lung tissue were analyzed using microcomputed tomography (micro-CT), and the lung coefficient and pulmonary capillary permeability were measured. Enzyme-linked immunosorbent assay were used to determine the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α, and reactive oxygen species. The morphology of mitochondria in type Ⅱ epithelial cells of lung tissue was observed using transmission electron microscopy; and the apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, mitofusin-2 (MFN2), phosphatase and tensin homolog (PTEN), PTEN-L, p62, and the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by Western blotting, and the ratio of LC3II/LC3I was calculated. Results: Compared with the EHS group, the survival rate of rats in the EHS + Parkin group was significantly higher. Their lung coefficient and pulmonary vascular permeability decreased and the pathological changes were significantly alleviated (P <0.05). Their levels of inflammatory factors and reactive oxygen species were significantly decreased (P <0.05), and the degree of mitochondrial swelling in pulmonary type II epithelial cells was alleviated. The apoptosis of lung tissue was alleviated, the colocalization of Pink1 and Parkin, LC3 and Tom20 was enhanced, and the ratio of LC3-II/LC3-I increased. The expression of Pink1, MFN2, PTEN-L, and p62 decreased, whereas the expression of PTEN was not significantly different from that in the EHS group (P >0.05). Conclusion: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying ALI in rats with EHS, and activation of Parkin overexpression-mediated mitophagy can alleviate ALI caused by EHS.http://www.sciencedirect.com/science/article/pii/S2667100X2400094XExertional heat strokeAcute lung injuryMitophagyPink1Parkin |
| spellingShingle | Ran Meng Zhengzhong Sun Ruxue Chi Yan Gu Yuxiang Zhang Jiaxing Wang Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke Journal of Intensive Medicine Exertional heat stroke Acute lung injury Mitophagy Pink1 Parkin |
| title | Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| title_full | Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| title_fullStr | Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| title_full_unstemmed | Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| title_short | Overexpression of Parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| title_sort | overexpression of parkin promotes the protective effect of mitochondrial autophagy on the lung of rats with exertional heatstroke |
| topic | Exertional heat stroke Acute lung injury Mitophagy Pink1 Parkin |
| url | http://www.sciencedirect.com/science/article/pii/S2667100X2400094X |
| work_keys_str_mv | AT ranmeng overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke AT zhengzhongsun overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke AT ruxuechi overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke AT yangu overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke AT yuxiangzhang overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke AT jiaxingwang overexpressionofparkinpromotestheprotectiveeffectofmitochondrialautophagyonthelungofratswithexertionalheatstroke |