Effect of acute moderate-intensity cycling on cfDNA levels considering menstrual cycle phases.

Introduction: We aimed to determine the effects of exercise on cell-free DNA (cfDNA) levels and concentration changes during the menstrual cycle in participants with regular menstrual cycles and no exercise habits. Methods: Eleven sedentary female students with regular menstrual cycles and ovulation performed bicycle exercises at 60% VO2max for 30 min during the menstrual, ovulatory, and luteal phases. Blood samples were collected before (Pre), immediately after (Post 0), 30 min after (Post 30), and 60 min after (Post 60) exercise. Blood concentrations of ovarian hormones, cfDNA, prostaglandin F2a (PGF2α), interleukin-6 (IL-6), and aromatase were evaluated. Results: Based on the concentration of ovarian hormones, seven individuals were finally analyzed. No significant phase difference was observed in cfDNA across all time points. cfDNA (menstrual phase: p = 0.028, ovulatory phase: p = 0.018, and luteal phase: p = 0.048) and aromatase concentrations (menstrual phase: p = 0.040, ovulatory phase: p = 0.039, and luteal phase: p = 0.045) significantly increased from Pre to Post 0 in all phases. Serum estradiol (E2) levels were significantly higher in the luteal phase at all time points than in the menstrual phase (Pre: p < 0.001, Post 0: p < 0.001, Post 30: p = 0.005, and Post 60: p = 0.011); however, serum progesterone (P4) levels were significantly higher in the luteal phase at all time points than in the menstrual (Pre: p < 0.001, Post 0: p < 0.001, Post 30: p < 0.001, and Post 60: p < 0.001) and ovulatory phases (Pre: p = 0.005, Post 0: p = 0.005, Post 30: p = 0.003, and Post 60: p = 0.003). E2 levels significantly increased from Pre to Post 0 in the ovulatory and luteal phases, whereas P4 levels increased in the luteal phase. Progesterone to estradiol level ratio (P4/E2) changes from Pre to Post 0 (%baseline) during the luteal phase were significantly negatively correlated (r = -0.82, p = 0.046) with the changes in cfDNA from Pre to Post 0. Furthermore, the repeated measures correlation between P4/E2 and cfDNA level showed a significant negative correlation in ovulatory and luteal phases. Discussion: The results indicate that while resting cfDNA levels are unlikely to be affected by a woman's menstrual cycle, the increase in cfDNA after exercise is higher in the ovulatory phase (when only E2 increases) and lower in the luteal phase (when E2 and P4 increase with exercise) compared to that in the menstrual phase (when E2 and P4 are in low levels), suggesting the contribution of increased ovarian hormone levels after exercise.

Cyclic-AMP response element binding protein (CREB) and microRNA miR-29b regulate renalase gene expression under catecholamine excess conditions.

AIMS: Renalase, a key mediator of cross-talk between kidneys and sympathetic nervous system, exerts protective roles in various cardiovascular/renal disease states. However, molecular mechanisms underpinning renalase gene expression remain incompletely understood. Here, we sought to identify the key molecular regulators of renalase under basal/catecholamine-excess conditions. MATERIALS AND METHODS: Identification of the core promoter domain of renalase was carried out by promoter-reporter assays in N2a/HEK-293/H9c2 cells. Computational analysis of the renalase core promoter domain, over-expression of cyclic-AMP-response-element-binding-protein (CREB)/dominant negative mutant of CREB, ChIP assays were performed to determine the role of CREB in transcription regulation. Role of the miR-29b-mediated-suppression of renalase was validated in-vivo by using locked-nucleic-acid-inhibitors of miR-29. qRT-PCR and Western-blot analyses measured the expression of renalase, CREB, miR-29b and normalization controls in cell lysates/ tissue samples under basal/epinephrine-treated conditions. KEY FINDINGS: CREB, a downstream effector in epinephrine signaling, activated renalase expression via its binding to the renalase-promoter. Physiological doses of epinephrine and isoproterenol enhanced renalase-promoter activity and endogenous renalase protein level while propranolol diminished the promoter activity and endogenous renalase protein level indicating a potential role of beta-adrenergic receptor in renalase gene regulation. Multiple animal models (acute exercise, genetically hypertensive/stroke-prone mice/rat) displayed directionally-concordant expression of CREB and renalase. Administration of miR-29b inhibitor in mice upregulated endogenous renalase expression. Moreover, epinephrine treatment down-regulated miR-29b promoter-activity/transcript levels. SIGNIFICANCE: This study provides evidence for renalase gene regulation by concomitant transcriptional activation via CREB and post-transcriptional attenuation via miR-29b under excess epinephrine conditions. These findings have implications for disease states with dysregulated catecholamines.

Effects of lactate administration on hypertrophy and mTOR signaling activation in mouse skeletal muscle.

Lactate is a metabolic product of glycolysis and has recently been shown to act as a signaling molecule that induces adaptations in oxidative metabolism. In this study, we investigated whether lactate administration enhanced muscle hypertrophy and protein synthesis responses during resistance exercise in animal models. We used male ICR mice (7-8 weeks old) were used for chronic (mechanical overload induced by synergist ablation: [OL]) and acute (high-intensity muscle contraction by electrical stimulation: [ES]) resistance exercise models. The animals were intraperitoneally administrated a single dose of sodium lactate (1 g/kg of body weight) in the ES study, and once a day for 14 consecutive days in the OL study. Two weeks of mechanical overload increased plantaris muscle wet weight (main effect of OL: p < 0.05) and fiber cross-sectional area (main effect of OL: p < 0.05), but those were not affected by lactate administration. Following the acute resistance exercise by ES, protein synthesis and phosphorylation of p70 S6 kinase and ribosomal protein S6, which are downstream molecules in the anabolic signaling cascade, were increased (main effect of ES: p < 0.05), but lactate administration had no effect. This study demonstrated that exogenous lactate administration has little effect on the muscle hypertrophic response during resistance exercise using acute ES and chronic OL models. Our results do not support the hypothesis that elevated blood lactate concentration induces protein synthesis responses in skeletal muscle.

Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury.

Excess activation of circulating xanthine oxidoreductase (XOR) may contribute to the pathogenesis of widespread remote organ injury, including kidney injury. The purpose of this study was to determine the acute impact of marathon running on plasma XOR activity and to examine whether plasma XOR activity is associated with marathon-induced elevations in biomarkers of acute kidney injury (AKI). Twenty-three young men (aged 20-25 yr) who participated in the 38th Tsukuba Marathon were included. Blood and urine samples were collected before, immediately, 2 h (only blood sample), and 24 h after a full marathon run. Plasma XOR activity was evaluated using a highly sensitive assay utilizing a combination of [13C2,15N2] xanthine and liquid chromatography-triple quadrupole mass spectrometry. The levels of several AKI biomarkers, such as serum creatinine and urinary liver-type fatty acid-binding protein (L-FABP) were measured in each participant. Marathon running caused a transient elevation in plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid) as well as serum creatinine, urinary albumin, and urinary L-FABP levels. Immediately after the marathon, individual relative changes in plasma XOR activity were independently correlated with corresponding changes in serum creatinine and urinary L-FABP levels. In addition, the magnitude of marathon-induced elevation in plasma XOR activity and levels of purine degradation products were higher in individuals who developed AKI. These findings collectively suggest that marathon running substantially influences the purine metabolism pathway including XOR activity. Moreover, activated circulating XOR can be partly associated with elevated biomarkers of AKI after marathon running.NEW & NOTEWORTHY This study is the first to show marathon running transiently increases plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid), and further to demonstrate that activated plasma XOR may contribute to marathon-induced elevations in biomarkers of AKI. These findings significantly extend our prior knowledge of the purine metabolic pathway and several AKI biomarkers under strenuous exercise conditions.

Long-Term Habitual Exercise and Combination of ß-Hydroxy-ß-Methylbutyrate plus Black Ginger Alter the Autophagy and Mitochondria Related Genes in SAMP8 Mice.

Muscle mass and strength decrease with aging; however, habitual exercise can maintain muscle health. ß-Hydroxy-ß-methyl butyrate calcium (HMB) and black ginger (BG) improve muscle protein metabolism and energy production. Combining these two molecules, which have similar effects, may have a synergistic effect. Senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of muscle aging. Therefore, we explored how the combination of habitual exercise, HMB, and BG affected muscle aging. We used 28-wk-old (28w) SAMP8 mice divided into six groups: 28 wk (28w), 44 wk (44w, Con), exercise (Ex), Ex+BG, Ex+HMB, and Ex+BG+HMB (Ex+Comb). Mice were required to run on a treadmill for 16 wk for 5 d per week. In 28w and 44w mice, grip strength tests and dissection were conducted. Muscle weight was measured, and qPCR and immunoblotting were conducted. Muscle mass and strength were declined in the 44w group. Exercise with HMB or BG alone had no effect, whereas muscle mass and strength were augmented in the Ex+Comb group. Similarly, levels of mitochondrial function- and biogenesis-related genes were increased. Autophagy-related protein (Atg3, 7, 16L1 and Beclin1) were altered in the Ex+Comb group. These results suggest that Ex+Comb affects autophagy. Overall, the combination of habitual exercise and HMB+BG may enhance muscle mass and strength by affecting the mitochondrial and autophagy systems in SAMP8.

Effect of a sulforaphane supplement on muscle soreness and damage induced by eccentric exercise in young adults: A pilot study.

OBJECTIVE: Excessive exercise increases the production of reactive oxygen species in skeletal muscles. Sulforaphane activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces a protective effect against oxidative stress. In a recent report, sulforaphane intake suppressed exercise-induced oxidative stress and muscle damage in mice. However, the effect of sulforaphane intake on delayed onset muscle soreness after eccentric exercise in humans is unknown. We evaluated the effect of sulforaphane supplement intake in humans regarding the delayed onset muscle soreness (DOMS) after eccentric exercise. RESEARCH METHODS & PROCEDURES: To determine the duration of sulforaphane supplementation, continuous blood sampling was performed and NQO1 mRNA expression levels were analyzed. Sixteen young men were randomly divided into sulforaphane and control groups. The sulforaphane group received sulforaphane supplements. Each group performed six set of five eccentric exercise with the nondominant arm in elbow flexion with 70% maximum voluntary contraction. We assessed muscle soreness in the biceps using the visual analog scale, range of motion (ROM), muscle damage markers, and oxidative stress marker (malondialdehyde; MDA). RESULTS: Sulforaphane supplement intake for 2 weeks increased NQO1 mRNA expression in peripheral blood mononuclear cells (PBMCs). Muscle soreness on palpation and ROM were significantly lower 2 days after exercise in the sulforaphane group compared with the control group. Serum MDA showed significantly lower levels 2 days after exercise in the sulforaphane group compared with the control group. CONCLUSION: Our findings suggest that sulforaphane intake from 2 weeks before to 4 days after the exercise increased NQO1, a target gene of Nrf2, and suppressed DOMS after 2 days of eccentric exercise.

Gene expression level of renalase in the skeletal muscles is increased with high-intensity exercise training in mice on a high-fat diet.

INTRODUCTION: Exercise training is beneficial for reducing obesity. In particular, exercise training can lower the catecholamine concentration in circulation. Renalase, whose expression was first confirmed in the kidneys, is a physiologically active substance that decomposes circulating catecholamines; additionally, it has been reported to be present in the skeletal muscles. The aim of this study was to clarify the expression of renalase in the skeletal muscles and kidneys after high-intensity exercise training in obese mice. MATERIAL AND METHODS: The mice were divided into four groups: normal diet and sedentary, normal diet and exercise training, high-fat diet and sedentary, and high-fat diet and exercise training, and the test was performed for 8 weeks. RESULTS: Body weight and skeletal muscle wet weight were reduced by high-fat diet intake but were rescued by training. Skeletal muscle renalase gene expression was significantly increased by exercise training. However, in the kidneys the gene expression of renalase was significantly increased by high-fat diet intake and exercise training. No significant changes were observed in the gene expression of catecholamine-degrading enzymes, catechol-O-methyltransferase and monoamine oxidase A and B. CONCLUSION: We demonstrated that exercise training increased the gene expression of renalase in the skeletal muscles and kidneys, thus lowering circulating catecholamine levels. This may lead to amelioration of obesity as catecholamines are lipolytic.

Plasma free metanephrine and normethanephrine levels correlated to plasma catecholamine after acute running in amateur runner.

BACKGROUND: Catecholamine is a typical index of exercise intensity, but it is difficult to detect. Plasma metanephrine (MN) and normethanephrine (NMN) levels are more stable than those of catecholamines. This study aimed to investigate plasma MN and NMN levels during acute exercise running in amateur runners. METHODS: Samples were collected from eight healthy male participants. They were either sedentary or running at low or high intensity for 30 min. Blood samples were collected under these conditions. Measurements taken included plasma adrenaline, noradrenaline, MN, and NMN. RESULTS: Plasma adrenaline levels increased after high-intensity exercise compared with sedentary subjects. Plasma noradrenaline, MN, and NMN levels increased after both low- and high-intensity exercise compared with sedentary subjects. In addition, these levels were also significantly higher at high intensity than at low intensity. Plasma adrenaline and noradrenaline levels were positively correlated with plasma free MN and NMN levels after acute running, respectively. CONCLUSION: This study revealed that plasma MN and NMN levels transiently increased depending on exercise intensity in amateur runners. In addition, plasma NMN levels are better markers than plasma MN levels because of their stronger correlation with plasma catecholamine levels.

Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model.

Progression of nonalcoholic steatohepatitis (NASH) is attributed to several factors, including inflammation and oxidative stress. In recent years, renalase has been reported to suppress oxidative stress, apoptosis and inflammation. A number of studies have suggested that renalase may be associated with protecting the liver from injury. The present study aimed to clarify the effects of renalase knockout (KO) in mice with NASH that were induced with a choline­deficient high­fat diet (CDAHFD) supplemented with 0.1% methionine. Wild type (WT) and KO mice (6­week­old) were fed a normal diet (ND) or CDAHFD for 6 weeks, followed by analysis of the blood liver function markers and liver tissues. CDAHFD intake was revealed to increase blood hepatic function markers, lipid accumulation and oxidative stress compared with ND, but no significant differences were observed between the WT and KO mice. However, in the KO­CDAHFD group, the Adgre1 and Tgfb1 mRNA levels were significantly higher, and α­SMA expression was significantly lower compared with the WT­CDAHFD group. Furthermore, the Gclc mRNA and phosphorylated protein kinase B (Akt) levels were significantly lower in the KO­ND group compared with the WT­ND group. The results of the current study indicated that as NASH progressed in the absence of renalase, oxidative stress, macrophage infiltration and TGF­ß expression were enhanced, while α­SMA expression in NASH may be partly suppressed due to the decreased phosphorylation of Akt level.

Renalase is localized to the small intestine crypt and expressed upon the activation of NF-κB p65 in mice model of fasting-induced oxidative stress.

AIMS: Renalase expression is regulated by Nuclear Factor (NF)-κB and hypoxia inducible factor (HIF)-1α, and antioxidative stress function in renal cells were reported. However, dynamics of renalase and localizes in intestine were remain unknown. We evaluated the effects of oxidative stress on renalase expression and localization using model of fasting induced oxidative stress and Caco-2 cell, and examined the its physiological effects. MAIN METHODS: 24 male mice were divided into three groups: Control (Con), 72 h fasting (Fast), and 24 h refeeding after fasting (Refeed). Jejunum and ileum were collected respectively. The structure of jejunum and ileum were observed by hematoxylin and eosin (HE) stain. The expression levels of carbonylated protein, renalase, NF-κB p65 and HIF-1α were measured by immunoblotting. Localization of renalase was observed by immunofluorescent. in vitro assay was performed using Caco-2 cell. Renalase was overexpressed using adenovirus. After that, Caco-2 cell was treated with 2 mM H2O2 for 30 min or 24 h. KEY FINDINGS: Renalase was increased in Fast and it was localized in crypt. HIF-1α did not increase, but NF-κB p65 increased in Fast. Renalase overexpression protects the Caco-2 cells against H2O2 induced oxidative stress. SIGNIFICANCE: Renalase was localized in crypt and increased in Fast. This increase suggested protect response to oxidative stress because undifferenced cells were localized in crypt and need to be protected. Actually, renalase protected Caco-2 cells against H2O2 induced oxidative stress. Small intestinal renalase expression was regulated by NF-κB p65 and was considered to be a defense mechanism against oxidative stress.

Denervation-induced muscle atrophy suppression in renalase-deficient mice via increased protein synthesis.

Denervation-induced muscle atrophy increases signaling through both protein degradation and synthesis pathways. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that inhibits apoptosis and inflammation and promotes cell survival. This study aimed to elucidate the effect of renalase on denervation-induced muscle atrophy. We used 7-week-old renalase knock-out (KO) mice (a model of denervation-induced muscle atrophy) and wild-type (WT) mice (KO: n = 6, weight = 20-26 g; WT: n = 5, weight = 19-23 g). After their left legs were denervated, these mice were killed 1 week later. KO mice had lighter muscle weight than the WT mice. We observed an increase in molecular signaling through protein degradation pathway as well as oxidative stress in denervated muscles compared with that in sham-operated muscles in both WT and KO mice. Additionally, we also observed the main effect of renalase in WT and KO mice. Mitochondrial oxidative phosphorylation protein content was lower in denervated muscles than in sham-operated muscles in both WT and KO mice. However, a significant difference was noted in the reaction with Akt and p70S6K (components of the protein synthesis pathway) between WT and KO mice. In conclusion, mice with renalase deficiency demonstrated an attenuation of denervation-induced muscle atrophy. This might be related to catecholamines because signaling through the protein synthesis pathway was increased following denervation in renalase KO mice compared with that in WT mice, despite showing no change in signaling through protein degradation pathways.

Relationship between early-onset muscle soreness and indirect muscle damage markers and their dynamics after a full marathon.

BACKGROUND/OBJECTIVE: Muscle soreness and damage occurs after completing a full marathon. Here we refer to muscle soreness induced by prolonged running as early-onset muscle soreness (EOMS) because muscle soreness and damage markers induced after prolonged running are different from delayed-onset muscle soreness (DOMS) and muscle damage markers induced after eccentric contraction, such as resistance exercise. The dynamics and relationship between muscle damage markers and EOMS are unclear; therefore, in this study, we aimed to elucidate the relationship between EOMS and indirect muscle damage markers, and their dynamics after a full marathon. METHODS: The following measurements were performed in 19 subjects who completed a full marathon: perceived muscle soreness (using a numeric rating scale), thigh circumference (CIR), hip joint range of motion (ROM), jump height (JH) and muscle damage marker activities in the blood (CK, AST, LDH, ALD) before (Pre), after (Post) and every day for 4 days after a full marathon (D1-4). RESULTS: EOMS was induced, as determined by the numeric rating scale score peaking immediately after a full marathon. ROM and JH significantly decreased and all muscle damage markers significantly increased after a full marathon. Serum CK and AST peaked at D1. Serum LDH and ALD peaked at Post and D3. Each marker showed different dynamics. CIR significantly decreased after a full marathon. CONCLUSION: Muscle soreness peaked and muscle damage markers in the blood showed different dynamics after a full marathon. In other words, this is different from DOMS.

LDH isoenzyme 5 is an index of early onset muscle soreness during prolonged running.

BACKGROUND: Muscle soreness is also induced during prolonged running such as a full marathon, and muscle soreness and increased damage markers are detected immediately after such a running. We named this muscle soreness, early onset muscle soreness (EOMS). Additionally, lactate dehydrogenase (LDH) level which has some isoenzyme is increased immediately after prolonged exercise. However, it is unclear that EOMS is related to muscle damage markers on prolonged running. This study aimed to determine at which point EOMS, and muscle damage markers are related to EOMS during prolonged running. METHODS: We studied 11 male subjects who habitually perform aerobic exercise. They ran 30 km at 90% of ventilatory threshold intensity. Every 10 km, we estimated perceived muscle soreness, and sampled blood to measure muscle and liver damage, inflammation, and oxidative stress (d-ROM and BAP) markers. RESULTS: Muscle soreness score lower limbs were significantly appeared at 20 km compared to that at 0 km. Serum lactate dehydrogenase (LDH) level increased at 30 km compared to that at 0 km. LDH isoenzymes 3, 4, and 5, and neutrophils significantly increased at 30 km compared to those at 0 km. Serum LDH isoenzyme 5 and change in aspartate aminotransferase significantly increased at 20 km. In addition, there was a significant correlation between the thigh NRS and amount of serum LDH isoenzyme 5 from 0 km to 20 km. d-ROM and BAP increased at 10 km compared to those at 0 km. CONCLUSIONS: EOMS started to occur at 20 km during a 30 km running task. Our data suggest that LDH isoenzyme 5 is a marker of occurrence in EOMS during prolonged running.

Moderate-intensity exercise increases renalase levels in the blood and skeletal muscle of rats.

Renalase is predominantly expressed in the kidney, where it plays a role in catecholamine metabolism and blood pressure regulation. Moderate-intensity exercise (MEX) has been shown to increase the concentration of renalase in the blood and to reduce renal function in humans. Moreover, such exercise was also reported to increase catecholamine levels. Here, we examined renalase concentration in the blood and renalase expression levels in different organs after MEX in rats. Twelve male Wistar rats were made to run on a treadmill (MEX group) for 60 min at 20 m·min-1 , after resting for 15 min. The control group rats were euthanized after resting on the treadmill. Tissue and blood samples were analyzed using western blotting, real-time RT-PCR and ELISA. Overall, the concentrations of renalase in the blood were significantly higher in the MEX group than that in the control group. Renalase expression was decreased in the kidney after 60 min of exercise, whereas the expression of renalase mRNA and protein in the extensor digitorum longus and plantaris muscles, respectively, increased after exercise. However, the expression of renalase in the other tissues examined did not change after acute exercise. In conclusion, we report that MEX for 60 min increases both renalase concentration in the blood and its expression in skeletal muscle.

Detection of Transgenes in Gene Delivery Model Mice by Adenoviral Vector Using ddPCR.

With the rapid progress of genetic engineering and gene therapy, the World Anti-Doping Agency has been alerted to gene doping and prohibited its use in sports. However, there is no standard method available yet for the detection of transgenes delivered by recombinant adenoviral (rAdV) vectors. Here, we aim to develop a detection method for transgenes delivered by rAdV vectors in a mouse model that mimics gene doping. These rAdV vectors containing the mCherry gene was delivered in mice through intravenous injection or local muscular injection. After five days, stool and whole blood samples were collected, and total DNA was extracted. As additional experiments, whole blood was also collected from the mouse tail tip until 15 days from injection of the rAdv vector. Transgene fragments from different DNA samples were analyzed using semi-quantitative PCR (sqPCR), quantitative PCR (qPCR), and droplet digital PCR (ddPCR). In the results, transgene fragments could be directly detected from blood cell fraction DNA, plasma cell-free DNA, and stool DNA by qPCR and ddPCR, depending on specimen type and injection methods. We observed that a combination of blood cell fraction DNA and ddPCR was more sensitive than other combinations used in this model. These results could accelerate the development of detection methods for gene doping.

Influence of acute exercise on renalase and its regulatory mechanism.

AIMS: Renalase expression in the kidneys and liver is regulated by nuclear factor (NF)-κB, Sp1, and hypoxia-inducible factor (HIF)-1α. The dynamics of renalase expression in acute exercise, and its mechanism and physiological effects are unclear. We evaluated the effect of different exercise intensities on renalase expression and examined its mechanism and physiological effects. MAIN METHODS: 21 male Wistar rats ran for 30 min on a treadmill after resting for 15 min. The sedentary group rested on the treadmill while the exercise group ran for 30 min at 10 or 30 m/min. Skeletal muscles, the kidney, heart, liver, and blood samples were collected after exercise. The expression of renalase and phosphate IkB-α and Akt was measured by western blotting, while HIF-1α, Sp1, MuRF-1, and MAFbx were measured in the skeletal muscle by real-time RT-PCR. KEY FINDINGS: Renalase expression in skeletal muscles increased after acute exercise, while its expression in the kidneys, heart, and liver decreased. NF-κB regulated renalase expression in the plantaris muscle and that of HIF-1α in the soleus muscle. Phosphate Akt in the plantaris muscle significantly increased in the 30 m/min group compared with that in the sedentary group. MuRF-1 in the plantaris did not change between these groups. SIGNIFICANCE: Renalase expression in skeletal muscles increased after acute exercise but decreased in other tissues. This increase may be a response to exercise-induced oxidative stress. Furthermore, NF-κB in the plantaris muscle may mainly regulate renalase expression, and support a relationship with the cell protective effects of renalase.