Markers of inflammation, proteolysis, and apoptosis in ESRD

Raj, Dominic S.; Shah, Hemangini; Shah, Vallabh O.; Ferrando, Arny A.; Bankhurst, Arthur D.; Wolfe, Robert R.; Zager, Philip G.

doi:10.1053/j.ajkd.2003.08.022

Cited by 61 publications

(49 citation statements)

References 30 publications

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“…IL-6 plays a major role in regulating protein breakdown in inflammatory states (41). We found a significant correlation between plasma IL-6 levels and caspase-3, ubiquitin, and branched-chain keto acid dehydrogenase-E 2 gene expression in the skeletal muscle of the patients (38). Thus cytokines may also play a role in mediating the increased protein catabolism during HD through activation of the ubiquitin-proteasome pathway (32).…”

Section: Discussionmentioning

confidence: 93%

“…Our study also shows that ESRD patients are in a state of metabolic equilibrium despite the uremia before dialysis. The possible mechanisms for protein conservation in CRF are downregulation of genes promoting protein catabolism (38), correction of metabolic acidosis, and adequate protein and calorie intake by the participants. Berkelhammer et al (6), using an L-[1-…”

Section: Discussionmentioning

confidence: 99%

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Protein turnover and amino acid transport kinetics in end-stage renal disease

Raj¹,

Zager²,

Shah³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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. Protein turnover and amino acid transport kinetics in end-stage renal disease. Am J Physiol Endocrinol Metab 286: E136-E143, 2004. First published September 16, 2003 10.1152/ ajpendo.00352.2003.-Protein and amino acid metabolism is abnormal in end-stage renal disease (ESRD). Protein turnover is influenced by transmembrane amino acid transport. The effect of ESRD and hemodialysis (HD) on intracellular amino acid transport kinetics is unknown. We studied intracellular amino acid transport kinetics and protein turnover by use of stable isotopes of phenylalanine, leucine, lysine, alanine, and glutamine before and during HD in six ESRD patients. Data obtained from amino acid concentrations and enrichment in the artery, vein, and muscle compartments were used to calculate intracellular amino acid transport and muscle protein synthesis and catabolism. Fractional muscle protein synthesis (FSR) was estimated by the precursor product approach. Despite a significant decrease in the plasma concentrations of amino acids in the artery and vein during HD, the intracellular concentrations remained stable. Outward transport of the amino acids was significantly higher than the inward transport during HD. FSR increased during HD (0.0521 Ϯ 0.0043 vs. 0.0772 Ϯ 0.0055%/h, P Ͻ 0.01). Results derived from compartmental modeling indicated that both protein synthesis (118.3 Ϯ 20.6 vs. 146.5 Ϯ 20.6 nmol⅐min Ϫ1 ⅐100 ml leg Ϫ1 , P Ͻ 0.01) and catabolism (119.8 Ϯ 18.0 vs. 174.0 Ϯ 14.2 nmol⅐min Ϫ1 ⅐100 ml leg Ϫ1 , P Ͻ 0.01) increased during HD. However, the intradialytic increase in catabolism exceeded that of synthesis (57.8 Ϯ 13.8 vs. 28.0 Ϯ 8.5%, P Ͻ 0.05). Thus HD alters amino acid transport kinetics and increases protein turnover, with net increase in protein catabolism. protein synthesis; protein catabolism; amino acid metabolism; hemodialysis LOSS OF LEAN BODY MASS is common in patients with end-stage renal disease (ESRD) (47). The etiology of uremic cachexia remains elusive and controversial. However, malnutrition is one of the most important predictors of increased mortality and morbidity. Accumulation of uremic toxins, anorexia, metabolic acidosis, loss of metabolizing renal tissue, perturbations in the production of or responsiveness to catabolic and anabolic hormones, and activation of cytokines act in concert to contribute to the muscle wasting in uremia (4, 5). A healthy adult synthesizes and degrades ϳ200 g of tissue protein every day; consequently, even a small but sustained change in protein balance will have a major impact on lean body mass (44). Augmented protein catabolism and/or decreased protein synthesis in ESRD could be the cause of uremic cachexia. A number of investigators have observed that protein turnover is abnormal in ESRD. Metabolic acidosis that accompanies chronic renal failure (CRF) is known to promote protein catabolism (3, 39). However, the effect of uremia per se on protein turnover independent of metabolic acidosis has not been rigorously studied. Also, the effect of hemodialysis on protein turnover r...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Protein turnover and amino acid transport kinetics in end-stage renal disease

Raj¹,

Zager²,

Shah³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…Lack of a decrease in protein catabolism, despite an increase in plasma insulin and abundant amino acid supply during HDϩAA, could be due to a concomitant increase in plasma cortisol (37) and proinflammatory cytokine activation (19). Preliminary evidence from our laboratory has shown that IL-6 is released from skeletal muscle (41) and may mediate muscle protein catabolism (42,43). Biolo et al (2) demonstrated that pentoxifylline decreases whole body proteolysis in patients with chronic renal failure, possibly through inhibition of tumor necrosis factor-␣.…”

Section: Discussionmentioning

confidence: 99%

“…There was an unbalanced increase in muscle protein catabolism (F mo ) compared with synthesis (F om ) during HD-O for phenylalanine (16.7 We further substantiated increased protein breakdown during HDϩAA by demonstrating an increase in 14-kDa carboxyterminal actin in the muscle. Muscle protein catabolism involves activation of the ubiquitin-proteasome system (43). The initial rate-limiting step in muscle protein breakdown is activation of caspase-3, which cleaves actomyosin to create a substrate that is degraded by the ubiquitin-proteasome system (14).…”

Section: Discussionmentioning

confidence: 99%

“…Our group reported that amino acid depletion by HD promotes protein catabolism to maintain the plasma and intracellular amino acid concentrations (39). Our group also has shown that abnormal protein turnover in ESRD could be due to altered amino acid transport kinetics (40) and that interleukin-6 (IL-6) plays a key role in HD-induced muscle protein catabolism (42,43). Amino acid utilization for protein synthesis is impaired in patients with chronic renal failure (11).…”

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confidence: 99%

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Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

Raj

Adeniyi²,

Dominic³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

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Characterization and Regulation of Mechanical Loading‐Induced Compensatory Muscle Hypertrophy

Adams

Bamman

2012

Comprehensive Physiology

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In mammalian systems, skeletal muscle exists in a dynamic state that monitors and regulates the physiological investment in muscle size to meet the current level of functional demand. This review attempts to consolidate current knowledge concerning development of the compensatory hypertrophy that occurs in response to a sustained increase in the mechanical loading of skeletal muscle. Topics covered include: defining and measuring compensatory hypertrophy, experimental models, loading stimulus parameters, acute responses to increased loading, hyperplasia, myofiber-type adaptations, the involvement of satellite cells, mRNA translational control, mechanotransduction, and endocrinology. The authors conclude with their impressions of current knowledge gaps in the field that are ripe for future study.

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Markers of inflammation, proteolysis, and apoptosis in ESRD

Cited by 61 publications

References 30 publications

Protein turnover and amino acid transport kinetics in end-stage renal disease

Protein turnover and amino acid transport kinetics in end-stage renal disease

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

Characterization and Regulation of Mechanical Loading‐Induced Compensatory Muscle Hypertrophy

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