Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis
The beneficial effects of Korean red ginseng extract (KRGE) on the central nervous system (CNS) have been reported. Among the CNS cells, astrocytes possess robust antioxidative properties and regenerative potential. Under physiological conditions, biliverdin reductase A (BVR-A) converts biliverdin (...
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MDPI AG
2022-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/9/1742 |
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| author | Sunhong Moon Chang-Hee Kim Jinhong Park Minsu Kim Hui Su Jeon Young-Myeong Kim Yoon Kyung Choi |
| author_facet | Sunhong Moon Chang-Hee Kim Jinhong Park Minsu Kim Hui Su Jeon Young-Myeong Kim Yoon Kyung Choi |
| author_sort | Sunhong Moon |
| collection | DOAJ |
| description | The beneficial effects of Korean red ginseng extract (KRGE) on the central nervous system (CNS) have been reported. Among the CNS cells, astrocytes possess robust antioxidative properties and regenerative potential. Under physiological conditions, biliverdin reductase A (BVR-A) converts biliverdin (a heme oxygenase metabolite) into bilirubin, a major natural and potent antioxidant. We found that KRGE enhanced BVR-A in astrocytes in the fimbria region of the adult mouse hippocampus under physiological conditions. KRGE-induced BVR-A expression and subsequent bilirubin production were required for changes in mitochondrial membrane potential, mitochondrial mass, and oxidative phosphorylation through liver kinase B1 (LKB1), estrogen-related receptor α (ERRα), and sirtuin (SIRT1 and SIRT5) in astrocytes. However, BVR-A did not affect the KRGE-induced expression of AMP-activated protein kinase α (AMPKα). The KRGE-stimulated BVR-A–LKB1–SIRT1–ERRα pathway regulates the levels of mitochondria-localized proteins such as SIRT5, translocase of the outer mitochondrial membrane 20 (Tom20), Tom22, cytochrome c (Cyt c), and superoxide dismutase 2 (SOD2). Increased Tom20 expression in astrocytes of the hippocampal fimbria region was observed in KRGE-treated mice. KRGE-induced expression of Cyt c and SOD2 was associated with the Tom20/Tom22 complex. Taken together, KRGE-induced bilirubin production is required for enhanced astrocytic mitochondrial function in an LKB1-dependent and AMPKα-independent manner under physiological conditions. |
| first_indexed | 2024-03-10T00:52:45Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T00:52:45Z |
| publishDate | 2022-09-01 |
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| series | Antioxidants |
| spelling | doaj.art-4729be1bf67c4904904466395ec1cb292023-11-23T14:48:10ZengMDPI AGAntioxidants2076-39212022-09-01119174210.3390/antiox11091742Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα AxisSunhong Moon0Chang-Hee Kim1Jinhong Park2Minsu Kim3Hui Su Jeon4Young-Myeong Kim5Yoon Kyung Choi6Bio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05029, KoreaBio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaBio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaBio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, KoreaBio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaThe beneficial effects of Korean red ginseng extract (KRGE) on the central nervous system (CNS) have been reported. Among the CNS cells, astrocytes possess robust antioxidative properties and regenerative potential. Under physiological conditions, biliverdin reductase A (BVR-A) converts biliverdin (a heme oxygenase metabolite) into bilirubin, a major natural and potent antioxidant. We found that KRGE enhanced BVR-A in astrocytes in the fimbria region of the adult mouse hippocampus under physiological conditions. KRGE-induced BVR-A expression and subsequent bilirubin production were required for changes in mitochondrial membrane potential, mitochondrial mass, and oxidative phosphorylation through liver kinase B1 (LKB1), estrogen-related receptor α (ERRα), and sirtuin (SIRT1 and SIRT5) in astrocytes. However, BVR-A did not affect the KRGE-induced expression of AMP-activated protein kinase α (AMPKα). The KRGE-stimulated BVR-A–LKB1–SIRT1–ERRα pathway regulates the levels of mitochondria-localized proteins such as SIRT5, translocase of the outer mitochondrial membrane 20 (Tom20), Tom22, cytochrome c (Cyt c), and superoxide dismutase 2 (SOD2). Increased Tom20 expression in astrocytes of the hippocampal fimbria region was observed in KRGE-treated mice. KRGE-induced expression of Cyt c and SOD2 was associated with the Tom20/Tom22 complex. Taken together, KRGE-induced bilirubin production is required for enhanced astrocytic mitochondrial function in an LKB1-dependent and AMPKα-independent manner under physiological conditions.https://www.mdpi.com/2076-3921/11/9/1742liver kinase B1biliverdin reductaseantioxidantsbilirubinmitochondrial membrane potentialoxidative phosphorylation |
| spellingShingle | Sunhong Moon Chang-Hee Kim Jinhong Park Minsu Kim Hui Su Jeon Young-Myeong Kim Yoon Kyung Choi Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis Antioxidants liver kinase B1 biliverdin reductase antioxidants bilirubin mitochondrial membrane potential oxidative phosphorylation |
| title | Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis |
| title_full | Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis |
| title_fullStr | Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis |
| title_full_unstemmed | Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis |
| title_short | Induction of BVR-A Expression by Korean Red Ginseng in Murine Hippocampal Astrocytes: Role of Bilirubin in Mitochondrial Function via the LKB1–SIRT1–ERRα Axis |
| title_sort | induction of bvr a expression by korean red ginseng in murine hippocampal astrocytes role of bilirubin in mitochondrial function via the lkb1 sirt1 errα axis |
| topic | liver kinase B1 biliverdin reductase antioxidants bilirubin mitochondrial membrane potential oxidative phosphorylation |
| url | https://www.mdpi.com/2076-3921/11/9/1742 |
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