Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells
Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in cell membranes and mitochondria, which consist of the bilayer molecules. Targeting mitochondria to ameliorate inflammatory diseases by regulating mitochondrial metabolism has become possible and topical. Although AX...
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MDPI AG
2022-10-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/11/660 |
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| author | Luchuanyang Sun Sangeun Kim Ryoichi Mori Nobuyuki Miyaji Takeshi Nikawa Katsuya Hirasaka |
| author_facet | Luchuanyang Sun Sangeun Kim Ryoichi Mori Nobuyuki Miyaji Takeshi Nikawa Katsuya Hirasaka |
| author_sort | Luchuanyang Sun |
| collection | DOAJ |
| description | Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in cell membranes and mitochondria, which consist of the bilayer molecules. Targeting mitochondria to ameliorate inflammatory diseases by regulating mitochondrial metabolism has become possible and topical. Although AX has been shown to have anti-inflammatory effects in various cells, the mechanisms are quite different. In particular, the role of AX on mitochondrial metabolism in macrophages is still unknown. In this study, we investigated the effect of AX on mitochondria-mediated inflammation and its mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. AX attenuated the mitochondrial O<sub>2</sub><sup>−</sup> production and maintained the mitochondrial membrane potential, implying that AX preserved mitochondrial homeostasis to avoid LPS stimulation-induced mitochondrial dysfunction. Additionally, AX prevented the decrease in mitochondrial complexes I, II, and III, which were caused by LPS stimulation. Especially, AX inhibited the reduction in mitochondrial succinate dehydrogenase (SDH; complex II) activity and upregulated the protein and mRNA level of SDH complex, subunit B. Furthermore, AX blocked the IL-1β expression by regulating the SDH-HIF-1α axis and suppressed the energy shift from an OXPHOS phenotype to a glycolysis phenotype. These findings revealed important effects of AX on mitochondrial enzymes as well as on mitochondrial energy metabolism in the immune response. In addition, these raised the possibility that AX plays an important role in other diseases caused by SDH mutation and metabolic disorders. |
| first_indexed | 2024-03-09T18:54:50Z |
| format | Article |
| id | doaj.art-70578d1488fa4bdfaa782a2a41383921 |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T18:54:50Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-70578d1488fa4bdfaa782a2a413839212023-11-24T05:34:02ZengMDPI AGMarine Drugs1660-33972022-10-01201166010.3390/md20110660Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 CellsLuchuanyang Sun0Sangeun Kim1Ryoichi Mori2Nobuyuki Miyaji3Takeshi Nikawa4Katsuya Hirasaka5Graduate School of Fisheries and Environmental Sciences, Nagasaki University, Nagasaki 8528521, JapanDepartment of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 8528523, JapanDepartment of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 8528523, JapanToyo Koso Kagaku Co., Ltd., Chiba 2790041, JapanDepartment of Nutritional Physiology, Institute of Medical Nutrition, Tokushima University Medical School, Tokushima 7708503, JapanGraduate School of Fisheries and Environmental Sciences, Nagasaki University, Nagasaki 8528521, JapanAstaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in cell membranes and mitochondria, which consist of the bilayer molecules. Targeting mitochondria to ameliorate inflammatory diseases by regulating mitochondrial metabolism has become possible and topical. Although AX has been shown to have anti-inflammatory effects in various cells, the mechanisms are quite different. In particular, the role of AX on mitochondrial metabolism in macrophages is still unknown. In this study, we investigated the effect of AX on mitochondria-mediated inflammation and its mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. AX attenuated the mitochondrial O<sub>2</sub><sup>−</sup> production and maintained the mitochondrial membrane potential, implying that AX preserved mitochondrial homeostasis to avoid LPS stimulation-induced mitochondrial dysfunction. Additionally, AX prevented the decrease in mitochondrial complexes I, II, and III, which were caused by LPS stimulation. Especially, AX inhibited the reduction in mitochondrial succinate dehydrogenase (SDH; complex II) activity and upregulated the protein and mRNA level of SDH complex, subunit B. Furthermore, AX blocked the IL-1β expression by regulating the SDH-HIF-1α axis and suppressed the energy shift from an OXPHOS phenotype to a glycolysis phenotype. These findings revealed important effects of AX on mitochondrial enzymes as well as on mitochondrial energy metabolism in the immune response. In addition, these raised the possibility that AX plays an important role in other diseases caused by SDH mutation and metabolic disorders.https://www.mdpi.com/1660-3397/20/11/660astaxanthinmitochondrial ROSmitochondrial energy metabolismmitochondrial succinate dehydrogenasehypoxia-inducible factor-1αinterleukin-1β |
| spellingShingle | Luchuanyang Sun Sangeun Kim Ryoichi Mori Nobuyuki Miyaji Takeshi Nikawa Katsuya Hirasaka Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells Marine Drugs astaxanthin mitochondrial ROS mitochondrial energy metabolism mitochondrial succinate dehydrogenase hypoxia-inducible factor-1α interleukin-1β |
| title | Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells |
| title_full | Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells |
| title_fullStr | Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells |
| title_full_unstemmed | Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells |
| title_short | Astaxanthin Exerts Immunomodulatory Effect by Regulating SDH-HIF-1α Axis and Reprogramming Mitochondrial Metabolism in LPS-Stimulated RAW264.7 Cells |
| title_sort | astaxanthin exerts immunomodulatory effect by regulating sdh hif 1α axis and reprogramming mitochondrial metabolism in lps stimulated raw264 7 cells |
| topic | astaxanthin mitochondrial ROS mitochondrial energy metabolism mitochondrial succinate dehydrogenase hypoxia-inducible factor-1α interleukin-1β |
| url | https://www.mdpi.com/1660-3397/20/11/660 |
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