Fernández-Ortiz, MarisolSayed, Ramy K.A.Fernández-Martínez, JoséCionfrini, AntoniaAranda-Martínez, PaulaEscames, Germainede Haro, TomásAcuña-Castroviejo, Darío2022-05-202022-05-202020-11-27Fernández-Ortiz M, Sayed RKA, Fernández-Martínez J, Cionfrini A, Aranda-Martínez P, Escames G, et al. Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging. Antioxidants. 2020 Nov 27;9(12):1187http://hdl.handle.net/10668/3654Aging is a major risk for cardiovascular diseases (CVD). Age-related disorders include oxidative stress, mitochondria dysfunction, and exacerbation of the NF-κB/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 effects. 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 effects in cardiac autophagy during aging. The deficiency of the inflammasome affected Bax/Bcl2 ratio, but not p53 or caspase 9. The Nrf2-antioxidant pathway was also unaffected 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 effects 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MelatoninMitochondriaNLRP3 inflammasomeNrf2Heart ultrastructureApoptosisMitochondrial dynamicsMelatoninaMitocondriaCorazónInflamasomasFactor 2 Relacionado con NF-E2Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::MelatoninMedical Subject Headings::Anatomy::Cells::Cellular Structures::Subcellular Fractions::MitochondriaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::InflammasomesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic-Leucine Zipper Transcription Factors::NF-E2-Related Factor 2Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::AntioxidantsMedical Subject Headings::Diseases::Cardiovascular DiseasesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::AutophagyMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::AgingMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Stress, Physiological::Oxidative Stressresearch article33260800open access10.3390/antiox91211872076-3921PMC7760557