Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

He, Xiaoqing; Ma, Qiang

doi:10.4172/2155-6156.s7-002

Cited by 22 publications

(11 citation statements)

References 37 publications

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“…The tight association between NRF2-mediated redox regulation and apoptosis has been widely observed through loss-of-function approaches. In a streptozotocin-induced diabetes model, Nrf2 knockout mice exhibited more severe diabetes than wild-type mice, and evoked severe cardiomyopathy along with increased apoptosis, accelerated inflammatory responses, and heightened oxidative stress in hearts (He and Ma, 2012 ).…”

Section: Atropos: Cellular Senescence and Deathmentioning

confidence: 99%

NRF2 and the Moirai: Life and Death Decisions on Cell Fates

Yagishita

Chartoumpekis

Kensler

et al. 2023

Antioxidants & Redox Signaling

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Significance: The transcription factor NRF2 (NF-E2-related factor 2) plays an important role as a master regulator of the cellular defense system by activating transcriptional programs of NRF2 target genes encoding multiple enzymes related to cellular redox balance and xenobiotic detoxication. Comprehensive transcriptional analyses continue to reveal an ever-broadening range of NRF2 target genes, demonstrating the sophistication and diversification of NRF2 biological signatures beyond its canonical cytoprotective roles. Recent Advances: Accumulating evidence indicates that NRF2 has a strong association with the regulation of cell fates by influencing key processes of cellular transitions in the three major phases of the life cycle of the cell ( i.e. , cell birth, cell differentiation, and cell death). The molecular integration of NRF2 signaling into this regulatory program occurs through a wide range of NRF2 target genes encompassing canonical functions and those manipulating cell fate pathways. Critical Issues: A singular focus on NRF2 signaling for dissecting its actions limits in-depth understanding of its intersection with the molecular machinery of cell fate determinations. Compensatory responses of downstream pathways governed by NRF2 executed by a variety of transcription factors and multifactorial signaling crosstalk require further exploration. Future Directions: Further investigations using optimized in vivo models and active engagement of overarching approaches to probe the interplay of widespread pathways are needed to study the properties and capabilities of NRF2 signaling as a part of a large network within the cell fate regulatory domain. Antioxid. Redox Signal. 38, 684–708.

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Section: Atropos: Cellular Senescence and Deathmentioning

confidence: 99%

NRF2 and the Moirai: Life and Death Decisions on Cell Fates

Yagishita

Chartoumpekis

Kensler

et al. 2023

Antioxidants & Redox Signaling

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“…Meakin et al (20) and He and Ma (21) tested the effects of NRF2 activators on oxidative and inflammatory stress in both cultured cells and living animals, finding that they have a beneficial effect on diabetes. The inability of NRF2-deficient animals to deal with oxidative and inflammatory stresses is also a major problem.…”

Section: Discussionmentioning

confidence: 99%

Study of Nuclear Factor Erythroid Related Factor 2 Gene Polymorphism in Patients with Type 2 Diabetes Mellitus

Aly¹,

Younes²,

Ahmed³

et al. 2023

The Egyptian Journal of Hospital Medicine

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Background: The molecular mechanisms that downregulate the nuclear factor erythroid related factor 2 (NRF2) expression in addition to gene polymorphism among type 2 diabetes mellitus (T2DM) patients. Objective: To investigating possible association between NRF2 gene polymorphism with T2DM development. Patients and Methods: This case-control study included 81 persons who were categorized into three groups; The first group, made up of 27 healthy people, served as a control, group 2 consisted of twenty-seven type 2 diabetics without foot ulcers, and group 3 consisted of twenty-seven patients with diabetic foot ulcer who had type 2 diabetes. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to do genotyping of NRF2 (rs35652124) single nucleotide gene polymorphism. Results: Concerning NRF2 genotyping in the investigated groups, 18 (67%) of controls possessed the CC genotype, while 7 (26%) possessed the CT genotype, and 2 (7%) possessed the TT genotype. Eight (30%) of cases in the cases group had the CC genotype, while 13% had CT genotype and 48% had TT genotype. Cases had a far higher frequency of the CT and TT genotypes than controls did. In terms of NRF2 allele distribution, we found that although 43 (80%) of controls and 11 (20%) of controls carried the C allele, 29 (54%) of patients carried the C allele and 25 (46%) of cases carried the T allele. T2DM patients had a significantly greater frequency of T alleles than control subjects. Conclusion: Regarding NRF2 genotyping, our study revealed that TT genotypes and T alleles were statistically significantly higher among patients' group (diabetic with and without diabetic foot) compared to controls. NRF2 gene has a proper value in prediction of T2DM.

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“…Acting as a transcription factor, it mediates the redox disturbances induced by environmental or endogenous factors through modulating the expression of multiple antioxidant response element (MRE)-dependent genes (Ma, 2013). Besides, Nrf2 is anti-inflammatory and its deficiency results in inflammation in an experimental setting (Johnson et al, 2010;Rangasamy et al, 2004Rangasamy et al, , 2005Garbin et al, 2009;Cho et al, 2004;He & Ma, 2012). This may be explained by the observed inhibitory actions of Nrf2 on the NF-κB pathway and proinflammatory cytokine production (Li et al, 2008;Ma et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Application of dietary supplements in the prevention of type 2 diabetes-related cardiovascular complications

Jin

Arroo

2020

Phytochem Rev

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Type 2 diabetes, which accounts for the vast majority of diabetes worldwide is the result of a lowered sensitivity of the insulin receptors, resulting in impaired sugar metabolism is and chronic hyperglycaemia. There is no cure for type 2 diabetes, though some people with prediabetes and diabetes manage to reach and hold normal blood sugar levels, thus avoiding most of the complications that come with chronic hyperglycaemia; this is sometimes referred to as 'reversing diabetes'. A healthy diet, with sufficient amounts of fruits, nuts, and vegetables is positively correlated with maintaining glycaemic control and prevention of diabetes-related complications.Whereas many different dietary phytochemicals have been considered to play a role in the glycaemic control and in prevention of degenerative diseases, there is currently no consensus on a particular mode of action. In this review, a range of pre-clinical studies and intervention studies, including randomised double-blind, placebo controlled clinical studies, are considered that investigate the role of dietary compounds in the prevention of type 2 diabetesrelated complications. Three generic mechanisms of action can be discerned: compounds that reduce sugar uptake, compounds that restore insulin function, and compounds that attenuate the effects of oxidative stress and chronic inflammation. Particularly the latter has received wide attention in the form of activation of the Nrf2-antioxidant response element signalling pathway by various polyphenolic or triterpenoid compounds. Although individual reports may present models with clear looking signalling cascades, an overall review shows that many biologically active compounds in the human diet are pan assay interference substances that alter several cell functions simultaneously, which makes them less attractive for drug development.

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Disruption of Nrf2 Synergizes with High Glucose to Cause Heightened Myocardial Oxidative Stress and Severe Cardiomyopathy in Diabetic Mice

Cited by 22 publications

References 37 publications

NRF2 and the Moirai: Life and Death Decisions on Cell Fates

NRF2 and the Moirai: Life and Death Decisions on Cell Fates

Study of Nuclear Factor Erythroid Related Factor 2 Gene Polymorphism in Patients with Type 2 Diabetes Mellitus

Application of dietary supplements in the prevention of type 2 diabetes-related cardiovascular complications

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