Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy |
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| Affiliation: | 1. Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People''s Republic of China;2. Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Central North Road, Wenzhou 325035, People''s Republic of China;1. Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil;2. Programa de Pós-Graduação em Química (PPGQ), Universidade Federal de Mato Grosso (UFMT), Brazil;3. Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Universidade Federal de Mato Grosso (UFMT), Brazil;1. University of Wyoming College of Health Sciences, Laramie, WY 82071, USA;2. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China;3. Department of Food Science, University of Massachusetts Amherst, Amherst, MA 01003, USA;4. University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK;5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;6. Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia;7. Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;8. Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland 4111, Australia;9. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA;10. Life Sciences Institute and Departments of Molecular, Cellular and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA;11. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195 USA |
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| Abstract: | The macrophage is an innate immune response cell that plays an important role in the development of sepsis. Dexmedetomidine (DEX) is a sedation drug, which have anti-oxidative, anti-inflammatory and anti-apoptosis effects and can be used on sepsis patients in the ICU. However, its mechanisms of action remain poorly understood. PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine protein kinase that recognizes damaged mitochondria and leads to mitophagy. This study investigated the effects of DEX on Lipopolysaccharides(LPS)-induced macrophage injury and explained the underlying mechanisms. The results showed that LPS treatment caused mitochondrial damage, mitochondria-dependent apoptosis and PINK1-mediated mitophagy; at the same time, PINK1 has a protective effect on LPS-induced macrophage apoptosis and inflammation by mitophagy that eliminates dysfunctional mitochondria. DEX could promote the clearance of damaged mitochondria characterized by low Mitochondrial membrane potential (MMP) and high reactive oxygen species(ROS), thus exerting a protective effect in LPS treated macrophages, and PINK1 mediated mitophagy is required for this protective effect. |
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