Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging
| Autor: | Germaine Escames, Darío Acuña-Castroviejo, Paula Aranda-Martínez, Tomás de Haro, José Fernández-Martínez, Ramy K. A. Sayed, Marisol Fernández-Ortiz, Antonia Cionfrini |
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| Přispěvatelé: | [Fernández-Ortiz,M, Sayed,RKA, Fernández-Martínez,J, Cionfrini,A, Aranda-Martínez,P, Escames,G, Acuña-Castroviejo,D] Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain. [Sayed,RKA] Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt. [Escames,G, Acuña-Castroviejo,D] CIBERfes, Ibs. Granada, Granada, Spain. [de Haro,T, Acuña-Castroviejo,D] UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, Granada, Spain., This study was partially supported by grants from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Spain), through the projects, PI16-00519, PI19-01372, and CB16-10-00238 (Co-funded by European Regional Development Fund/European Social Fund 'Investing in your future'), and from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (CTS-101), Spain. M.F.-O. and J.F.-M. are supported by a FPU fellowship from the Ministerio de Educación, Spain. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Physiology
Clinical Biochemistry Factor 2 Relacionado con NF-E2 Apoptosis melatonin Mitochondrion medicine.disease_cause Biochemistry Melatonina Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antioxidants [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] heart ultrastructure Mitocondria Melatonin Caspase-9 biology Corazón integumentary system Cardiac muscle apoptosis Inflammasome Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::DNA-Binding Proteins::Basic-Leucine Zipper Transcription Factors::NF-E2-Related Factor 2 [Medical Subject Headings] Mitochondria mitochondria medicine.anatomical_structure NLRP3-inflammasome medicine.drug medicine.medical_specialty Inflamasomas Article Nrf2 Phenomena and Processes::Physiological Phenomena::Physiological Processes::Stress Physiological::Oxidative Stress [Medical Subject Headings] Internal medicine Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Aging [Medical Subject Headings] medicine Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy [Medical Subject Headings] Molecular Biology Diseases::Cardiovascular Diseases [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] business.industry Autophagy lcsh:RM1-950 Anatomy::Cells::Cellular Structures::Subcellular Fractions::Mitochondria [Medical Subject Headings] Cell Biology mitochondrial dynamics NLRP3 inflammasome Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] Endocrinology lcsh:Therapeutics. Pharmacology Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Inflammasomes [Medical Subject Headings] biology.protein Mitochondrial dynamics business Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Melatonin [Medical Subject Headings] Oxidative stress Heart ultrastructure |
| Zdroj: | Antioxidants, Vol 9, Iss 1187, p 1187 (2020) Antioxidants Volume 9 Issue 12 Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) Digibug. Repositorio Institucional de la Universidad de Granada instname |
| ISSN: | 2076-3921 |
| Popis: | Aging is a major risk for cardiovascular diseases (CVD). Age-related disorders include oxidative stress, mitochondria dysfunction, and exacerbation of the NF- B/NLRP3 innate immune response pathways. Some of the molecular mechanisms underlying these processes, however, remain unclear. This study tested the hypothesis that NLRP3 inflammasome plays a role in cardiac aging and melatonin is able to counteract its e ects. With the aim of investigating the impact of NLRP3 inflammasome and the actions and target of melatonin in aged myocardium, we analyzed the expression of proteins implied in mitochondria dynamics, autophagy, apoptosis, Nrf2-dependent antioxidant response and mitochondria ultrastructure in heart of wild-type and NLRP3-knockout mice of 3, 12, and 24 months-old, with and without melatonin treatment. Our results showed that the absence of NLRP3 prevented age-related mitochondrial dynamic alterations in cardiac muscle with minimal e ects in cardiac autophagy during aging. The deficiency of the inflammasome a ected Bax/Bcl2 ratio, but not p53 or caspase 9. The Nrf2-antioxidant pathway was also una ected by the absence of NLRP3. Furthermore, NLRP3-deficiency prevented the drop in autophagy and mice showed less mitochondrial damage than wild-type animals. Interestingly, melatonin treatment recovered mitochondrial dynamics altered by aging and had few e ects on cardiac autophagy. Melatonin supplementation also had an anti-apoptotic action in addition to restoring Nrf2-antioxidant capacity and improving mitochondria ultrastructure altered by aging. Instituto de Salud Carlos III (Ministerio de Economia y Competitividad, Spain) PI16-00519 PI19-01372 CB16-10-00238 European Regional Development Fund/European Social Fund "Investing in your future" Junta de Andalucía CTS-101 German Research Foundation (DFG) |
| Databáze: | OpenAIRE |
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