The Role of Nrf2 in Skeletal Muscle on Exercise Capacity

Kitaoka, Yu

doi:10.3390/antiox10111712

Cited by 20 publications

(23 citation statements)

References 60 publications

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“…However, under stress conditions, NFE2L2 translocates into the nucleus and binds to antioxidant response elements of the target cytoprotective genes. Studies using NFE2L2-deficient mice on a C57BL/6 background demonstrated that NFE2L2 is important for antioxidant enzymes in skeletal muscles [43]. Thus, we speculate that a similar role for this transcription regulator exists in the skeletal muscle of dairy cows.…”

Section: Antioxidant Responsementioning

confidence: 71%

Alterations in Skeletal Muscle mRNA Abundance in Response to Ethyl-Cellulose Rumen-Protected Methionine during the Periparturient Period in Dairy Cows

Thanh

Jiang

Wichasit

et al. 2022

Animals

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This study aimed to evaluate the effect of feeding ethyl cellulose rumen-protected methionine (RPM) on skeletal muscle mRNA abundance during the periparturient period. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or RPM diet. The RPM was supplied from −28 to 60 days in milk (DIM) at a rate of 0.09% (prepartum) or 0.10% (postpartum) of dry matter (DM), ensuring a Lys:Met in the metabolizable protein of ~2.8:1. Muscle biopsies were collected at −21, 1, and 21 DIM. Thirty-five target genes associated with nutrient metabolism and biochemical pathways were measured via RT-qPCR. The mRNA abundance of genes associated with amino acid (AA) transport (SLC7A8, SLC43A2), carnitine transport (SLC22A5), insulin signaling (IRS1), and antioxidant response (NFE2L2) had diet × time effect (p < 0.05) due to greater abundance in RPM versus CON cows, especially at 1 and 21 DIM. Members of the AA transport (SLC7A8, SLC25A29, SCL38A9), fatty acid β-oxidation (ACADVL), vitamin transport (SLC5A6, SLC19A2), mTOR pathway (AKT1 and mTOR), antioxidant response (KEAP1, CUL3), CDP-Choline pathway and arginine metabolism had overall greater abundance (p < 0.05) in RPM versus CON cows. Overall, data indicate that RPM can alter nutrient metabolism in the skeletal muscle around parturition partly through alterations in mRNA abundance.

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Section: Antioxidant Responsementioning

confidence: 71%

Alterations in Skeletal Muscle mRNA Abundance in Response to Ethyl-Cellulose Rumen-Protected Methionine during the Periparturient Period in Dairy Cows

Thanh

Jiang

Wichasit

et al. 2022

Animals

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“…NFκB activity can be increased by ROSP but also by several other stimuli such as free fatty acids (FFA), advanced glycation products, and inflammatory cytokines induced by oxidative stress [ 19 ]. On the other way, high levels of ROSP activate the nuclear factor, erythroid 2-like 2 (Nrf2) pathway leading to increased transcription of genes coding for antioxidant proteins, and consequently inducing the antioxidant ROSP-fighting effects [ 76 ].…”

Section: Oxidative Stress and Inflammation: Two Essential Harmsmentioning

confidence: 99%

Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises

et al. 2022

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Today, inactivity and high-calorie diets contribute to the development of obesity and premature aging. In addition, the population of elderly people is growing due to improvements in healthcare management. Obesity and aging are together key risk factors for non-communicable diseases associated with several co-morbidities and increased mortality, with a major impact on skeletal muscle defect and/or poor muscle mass quality. Skeletal muscles contribute to multiple body functions and play a vital role throughout the day, in all our activities. In our society, limiting skeletal muscle deterioration, frailty and dependence is not only a major public health challenge but also a major socio-economic issue. Specific diet supplementation with natural chemical compounds such as grape polyphenols had shown to play a relevant and direct role in regulating metabolic and molecular pathways involved in the prevention and treatment of obesity and aging and their related muscle comorbidities in cell culture and animal studies. However, clinical studies aiming to restore skeletal muscle mass and function with nutritional grape polyphenols supplementation are still very scarce. There is an urgent need for clinical studies to validate the very encouraging results observed in animal models.

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“…In this fashion, Nrf2 is closely tied to muscular endurance against ROS and other associated oxidative byproducts of myocyte mitochondrial respiration. Within skeletal muscle itself, Nrf2 is part of the antioxidant response to ROS generated by aerobic respiration within striated myocytes and helps to reduce citrate synthase and COX-mediated inflammation [ 101 ]. In cases of exercise, muscle contractions (100 and 50 Hz) and long periods of aerobic exertion have been found to stimulate Nrf2 response [ 101 ].…”

Section: Clinical Nrf2 Modulatorsmentioning

confidence: 99%

“…Within skeletal muscle itself, Nrf2 is part of the antioxidant response to ROS generated by aerobic respiration within striated myocytes and helps to reduce citrate synthase and COX-mediated inflammation [ 101 ]. In cases of exercise, muscle contractions (100 and 50 Hz) and long periods of aerobic exertion have been found to stimulate Nrf2 response [ 101 ]. So why does exercise-mediated Nrf2 elevation prevent cardiomyopathy instead of possibly promoting it as seen with exogenous compounds?…”

Section: Clinical Nrf2 Modulatorsmentioning

confidence: 99%

Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation

Mathis

Kato

Hiramatsu

2022

Cells

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.

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The Role of Nrf2 in Skeletal Muscle on Exercise Capacity

Cited by 20 publications

References 60 publications

Alterations in Skeletal Muscle mRNA Abundance in Response to Ethyl-Cellulose Rumen-Protected Methionine during the Periparturient Period in Dairy Cows

Alterations in Skeletal Muscle mRNA Abundance in Response to Ethyl-Cellulose Rumen-Protected Methionine during the Periparturient Period in Dairy Cows

Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises

Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation

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