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Article

Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging

1
Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, Spain
2
Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, Egypt
3
CIBERfes, Ibs. Granada, 18016 Granada, Spain
4
UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, 18016 Granada, Spain
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(12), 1187; https://doi.org/10.3390/antiox9121187
Received: 29 October 2020 / Revised: 14 November 2020 / Accepted: 23 November 2020 / Published: 27 November 2020
(This article belongs to the Special Issue The Antioxidant Effect of Melatonin on Mitochondrial Network)
Aging 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. View Full-Text
Keywords: melatonin; mitochondria; NLRP3 inflammasome; Nrf2; heart ultrastructure; apoptosis; mitochondrial dynamics melatonin; mitochondria; NLRP3 inflammasome; Nrf2; heart ultrastructure; apoptosis; mitochondrial dynamics
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MDPI and ACS Style

Fernández-Ortiz, M.; Sayed, R.K.A.; Fernández-Martínez, J.; Cionfrini, A.; Aranda-Martínez, P.; Escames, G.; de Haro, T.; Acuña-Castroviejo, D. Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging. Antioxidants 2020, 9, 1187. https://doi.org/10.3390/antiox9121187

AMA Style

Fernández-Ortiz M, Sayed RKA, Fernández-Martínez J, Cionfrini A, Aranda-Martínez P, Escames G, de Haro T, Acuña-Castroviejo D. Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging. Antioxidants. 2020; 9(12):1187. https://doi.org/10.3390/antiox9121187

Chicago/Turabian Style

Fernández-Ortiz, Marisol, Ramy K. A. Sayed, José Fernández-Martínez, Antonia Cionfrini, Paula Aranda-Martínez, Germaine Escames, Tomás de Haro, and Darío Acuña-Castroviejo. 2020. "Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging" Antioxidants 9, no. 12: 1187. https://doi.org/10.3390/antiox9121187

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