DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy
Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) h...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5675 |
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| author | Jinglong Chen Danping Wang Yibo Zong Xiaojing Yang |
| author_facet | Jinglong Chen Danping Wang Yibo Zong Xiaojing Yang |
| author_sort | Jinglong Chen |
| collection | DOAJ |
| description | Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H<sub>2</sub>O<sub>2</sub>-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H<sub>2</sub>O<sub>2</sub> and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl<sub>4</sub> and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy. |
| first_indexed | 2024-03-10T11:00:07Z |
| format | Article |
| id | doaj.art-0a3edfd56db8461688ab89167d39c045 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:00:07Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0a3edfd56db8461688ab89167d39c0452023-11-21T21:31:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211567510.3390/ijms22115675DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated MitophagyJinglong Chen0Danping Wang1Yibo Zong2Xiaojing Yang3MOE Joint Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing 210095, ChinaOxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H<sub>2</sub>O<sub>2</sub>-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H<sub>2</sub>O<sub>2</sub> and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl<sub>4</sub> and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.https://www.mdpi.com/1422-0067/22/11/5675oxidative stressliver injuryDHAmitophagyERK1/2 signaling |
| spellingShingle | Jinglong Chen Danping Wang Yibo Zong Xiaojing Yang DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy International Journal of Molecular Sciences oxidative stress liver injury DHA mitophagy ERK1/2 signaling |
| title | DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy |
| title_full | DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy |
| title_fullStr | DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy |
| title_full_unstemmed | DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy |
| title_short | DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy |
| title_sort | dha protects hepatocytes from oxidative injury through gpr120 erk mediated mitophagy |
| topic | oxidative stress liver injury DHA mitophagy ERK1/2 signaling |
| url | https://www.mdpi.com/1422-0067/22/11/5675 |
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