2 research outputs found
Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging
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
CB16-10-00238European Regional Development Fund/European Social Fund "Investing in your future"Junta de Andalucía
CTS-101German Research Foundation (DFG