Redox regulation by NRF2 in aging and disease

Schmidlin, Cody J.; Dodson, Matthew; Madhavan, Lalitha; Zhang, Donna D.

doi:10.1016/j.freeradbiomed.2019.01.016

Cited by 319 publications

(261 citation statements)

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“…In the present study, we also evaluated Nrf2, a master regulator of cellular redox homeostasis (Schmidlin et al, 2019), and HO-1, one of the key enzymes that suppresses oxidative stress and may contribute to cardioprotection (Cao et al, 2015). We observed that Nrf2 was moderately/strongly expressed in the cytoplasm of lean cardiomyocytes (Figure 3A), but shows significantly decreased expression in ob/ob heart, reaching only very weak/weak expression ( Figure 3B).…”

Section: Heart Oxidative Stress Evaluationmentioning

confidence: 82%

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

et al. 2020

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Integrative Physiology, a section of the journal Frontiers in PhysiologyObesity is a worldwide epidemic disease that induces important structural and functional changes to the heart and predisposes a patient to devastating cardiac complications. Sirtuin1 (SIRT1) has been found to have roles in regulating cardiac function, but whether it can help in cardioprotection is not clear. The aim of the present study was to determine whether melatonin, by modulating SIRT1 and in turn mitochondria signaling, may alleviate obesity-induced cardiac injuries. We investigated 10 lean control mice and 10 leptin-deficient obese mice (ob/ob) orally supplemented with melatonin for 8 weeks, as well as equal numbers of age-matched lean and ob/ob mice that did not receive melatonin. Hearts were evaluated using multiple parameters, including biometric values, morphology, SIRT1 activity and expression of markers of mitochondria biogenesis, oxidative stress, and inflammation. We observed that ob/ob mice experienced significant heart hypertrophy, infiltration by inflammatory cells, reduced SIRT1 activity, altered mitochondrial signaling and oxidative balance, and overexpression of inflammatory markers. Notably, melatonin supplementation in ob/ob mice reverted these obesogenic heart alterations. Melatonin prevented heart remodeling caused by obesity through SIRT1 activation, which, together with mitochondrial pathways, reduced oxidative stress and inflammation.Homogenized heart tissues were adequately processed for the quantitative measurement of natriuretic peptides type-B (BNP) protein level using a specific ELISA Kit (Novus Biologicals, Abingdon, United Kingdom), according to the manufacturer's Frontiers in Physiology | www.frontiersin.org

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Section: Heart Oxidative Stress Evaluationmentioning

confidence: 82%

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

et al. 2020

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“…In fact, abnormal protein S-glutathionylation is related to diverse cellular detrimental changes, including protein aggregation, protein degradation, apoptosis and mitochondrial dysfunction [215]. A thiol redox system consisting of the glutathione system (glutathione/glutathione reductase/glutaredoxin/glutathione peroxidase) and the thioredoxin system (thioredoxin/thioredoxin peroxidase (peroxiredoxins)/sulfiredoxin/thioredoxin reductase [216] are believed to be the major players in redox status regulation [99,[217][218][219]. Further, the thioredoxin system is an important thiol/disulphide redox controller ensuring the redox homeostasis [220].…”

Section: Nad(p)h Quinone Oxidoreductase-1 Nqo1mentioning

confidence: 99%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

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“…This value is of the same magnitude to those found for genes that are very well known VDR targets: genes related to calcium homeostasis such as parvalbumin, the calcium exchanger NCX1 (SLC8A2-2) or related to antioxidant defence genes such as glutathione peroxidase, or NRF2 (NFE2L2-4) to cite a few [24,28]. It is interesting remembering that NRF2, in turn, activates the transcription of antioxidant and detoxifying genes such as catalase, superoxide dismutases or thioredoxin reductase [72]. In this context, the beneficial effects of calcitriol, as a natural NRF2 inducer, are in agreement with one of the emerging therapies for FA is based on the activation of NRF2 including sulphoraphane [73], dimethyl fumarate [74] or omaveloxolone [75,76].…”

Section: The Beneficial Role Of Calcitriol In Neurodegenerative Diseamentioning

confidence: 71%

Calcitriol increases frataxin levels and restores altered markers in cell models of Friedreich Ataxia

Britti¹,

Delaspre²,

Medina-Carbonero³

et al. 2020

Preprint

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Friedreich Ataxia (FA) is a neurodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein. In primary cultures of dorsal root ganglia neurons, we showed that frataxin depletion resulted in decreased levels of the mitochondrial calcium exchanger NCLX, neurite degeneration and apoptotic cell death. Here we describe that frataxin-deficient dorsal root ganglia neurons display low levels of ferredoxin 1, a mitochondrial Fe/S cluster-containing protein that interacts with frataxin and, interestingly, is essential for the synthesis of calcitriol, the active form of vitamin D. We provide data that calcitriol supplementation, used at nanomolar concentrations, is able to reverse the molecular and cellular markers altered in DRG neurons. Calcitriol is able to recover both ferredoxin 1 and NCLX levels and restores mitochondrial membrane potential. Accordingly, apoptotic markers and neurite degeneration are reduced resulting in cell survival recovery with calcitriol supplementation. All these beneficial effects would be explained by the finding that calcitriol is able to increase the mature frataxin levels in both, frataxin-deficient DRG neurons and cardiomyocytes;remarkably, this increase also occurs in lymphoblastoid cell lines derived from FA patients. In conclusion, these results provide molecular bases to consider calcitriol for an easy and affordable therapeutic approach for FA patients.

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Redox regulation by NRF2 in aging and disease

Cited by 319 publications

References 50 publications

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Calcitriol increases frataxin levels and restores altered markers in cell models of Friedreich Ataxia

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