Exercise in Maintenance Hemodialysis Patients Induces Transcriptional Changes in Genes Favoring Anabolic Muscle

Kopple, Joel D.; Wang, Huiyuan; Casaburi, Richard; Fournier, Mario; Lewis, Michael I.; Taylor, Wayne E.; Storer, Thomas W.

doi:10.1681/asn.2006070794

Cited by 143 publications

(146 citation statements)

References 39 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…[33][34][35] Exercise also increases the IGF-1 level in rats or mice with CKD as well as patients on hemodialysis. [36][37][38] This is relevant, because our results show that SGK-1 expression rises in response to treadmill running. Clinical studies suggest that exercise can reduce CKD-stimulated muscle wasting in patients.…”

Section: Discussionmentioning

confidence: 96%

Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3

Luo

Liang

et al. 2016

JASN

View full text Add to dashboard Cite

Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid-regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKDinduced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N-myc downstreamregulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD-induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD. 27: 279727: -280827: , 201627: . doi: 10.1681 CKD is frequently complicated by muscle atrophy because of stimulation of muscle protein degradation mediated by increased activity of both caspase-3 and the ubiquitin-proteasome system (UPS). 1 In muscles of rodents with CKD, caspase-3 stimulates cleavage of the complex structure of muscle protein to provide substrates for degradation by the UPS; it also stimulates proteolytic activity of the 26S proteasome. 2 The UPS can selectively degrade myofibrillar protein by stimulating the expression of ubiquitin E3 ligases, Atrogin1 and MuRF1. These ligases conjugate ubiquitin to proteins targeted for protein degradation, resulting in their degradation in the 26S proteasome. 3 Conditions associated with CKD that initiate loss of muscle mass include metabolic acidosis, inflammation, excess angiotensin II, myostatin expression, and insulin resistance. 1 J Am Soc Nephrol

show abstract

Section: Discussionmentioning

confidence: 96%

Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3

Luo

Liang

et al. 2016

JASN

View full text Add to dashboard Cite

show abstract

“…However, even though there is some evidence that the serious problem of muscle protein catabolism can be slowed by both strength and endurance exercise training in dialysis patients 2 , a number of studies have been unable to detect a net increase in lean body mass in response to such exercise. For example in a study 3 involving an 18 week exercise programme of aerobic or resistance training, alone or in combination, no significant change in body composition was observed. This implies that metabolic abnormalities in muscle during CKD may be limiting the anabolic effectiveness of exercise.…”

mentioning

confidence: 99%

Exercise-induced Biochemical Modifications in Muscle in Chronic Kidney Disease: Occult Acidosis as a Potential Factor Limiting the Anabolic Effect of Exercise

Clapp

Bevington

2011

Journal of Renal Nutrition

View full text Add to dashboard Cite

“…CKD, 9 but patients with severe CKD are frequently unable to withstand routine daily physical activity, let alone exercise training.…”

mentioning

confidence: 99%

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Klein

Hassounah

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Lowfrequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-g and IL-6) increased. Expression of the M1 macrophage marker IL-1b also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKDinduced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.

show abstract

Exercise in Maintenance Hemodialysis Patients Induces Transcriptional Changes in Genes Favoring Anabolic Muscle

Cited by 143 publications

References 39 publications

Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3

Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3

Exercise-induced Biochemical Modifications in Muscle in Chronic Kidney Disease: Occult Acidosis as a Potential Factor Limiting the Anabolic Effect of Exercise

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Contact Info

Product

Resources

About