Mechanisms stimulating protein degradation to cause muscle atrophy

Price, '; We, Mitch

doi:10.1097/00075197-199801000-00013

Cited by 28 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[12][13][14][15] Like patients with TID, the well-established non-obese diabetic (NOD) mouse, a model for spontaneous TID, is also susceptible to weight loss after diabetes onset. 16,17 The mechanism of wasting in the NOD mouse has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

et al. 2008

View full text Add to dashboard Cite

+T-cell subset lymphopenia was measured in wasting and non-wasting diabetic mice. Our data show that the mechanism of wasting in diabetic mice involves muscle atrophy, a significant increase in ubiquitin conjugation, and upregulation of the ubiquitin ligases, muscle RING finger 1 (MuRF1) and muscle atrophy F box/atrogin-1 (MAFbx), indicating cachexia. Moreover, fragmentation of DNA isolated from atrophied muscle tissue indicates apoptosis. While CD4 + T-cell lymphopenia is evident in all diabetic mice, CD4 + T cells that express a very low density of CD44 were significantly lost in wasting, but not non-wasting, diabetic mice. These data suggest that CD4 + T-cell subsets are not equally susceptible to cachexia-associated lymphopenia in diabetic mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

et al. 2008

View full text Add to dashboard Cite

show abstract

“…However, information regarding the signals and mechanisms by which metabolic acidosis might cause kidney hypertrophy is still incomplete, and whether these effects take place in the human kidney is unknown. A further complicating element is that the effects of acidosis on protein turnover rates vary in different tissue types, with catabolic events occurring in peripheral tissues and splanchnic organs (3,4).…”

mentioning

confidence: 99%

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Garibotto

Asioli²,

Robaudo³

et al. 2004

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ( 14 C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesis, so net protein leucine balance was markedly negative. In acidemic subjects, kidney protein degradation was no different from protein synthesis and was significantly lower (P Ͻ 0.05) than in controls. Kidney leucine oxidation was similar in both groups. Urinary ammonia excretion and total ammonia production were 186% and 110% higher, respectively, and more of the ammonia that was produced was shifted into urine (82% versus 65% in acidemic subjects versus controls). In all studies, protein degradation and net protein balance across the kidney were inversely related to urinary ammonia excretion and to the partition of ammonia into urine, but not to total ammonia production, arterial pH, , urinary flow, the uptake of glutamine by the kidney, or the ammonia released into the renal veins. The data show that response of the human kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect, which is likely induced by the increase in ammonia excretion and partition into the urine, is potentially responsible for kidney hypertrophy.Both in vitro and in vivo studies in animals have shown that metabolic acidosis causes several biochemical and morphologic changes in tubule cells, which are ultimately associated with kidney hypertrophy (1,2). Protein synthesis and degradation, the determinants of protein metabolism, are key factors in the hypertrophy process. However, information regarding the signals and mechanisms by which metabolic acidosis might cause kidney hypertrophy is still incomplete, and whether these effects take place in the human kidney is unknown. A further complicating element is that the effects of acidosis on protein turnover rates vary in different tissue types, with catabolic events occurring in peripheral tissues and splanchnic organs (3,4).Chronic acidosis causes several metabolic alterations in the renal proximal tubule, including increased H ϩ secretion (1,5), ammonia synthesis (6), and citrate reabsorption (6,7). These changes in tubule function are associated with changes in the activities of a number of proteins, including the apical membrane Na ϩ /H ϩ antiporter (7), glutaminase and glutamate dehydrogenase (8), and phosphoenolpyruvate carboxykinase (9), which may affect intracellular substrate availability for protein turnover, amino acid metabolism and/or transport, and gluconeogenesis. It has been shown that in tubule epithelial cells, the associated increase in ammonia production, rather than the acidosis per se, is responsible for favoring tubular hyper...

show abstract

“…In order to evaluate the fluctuation in tissue size, both rates of protein synthesis and protein degradation are important in order to understand the net protein flux. Protein degradation is important to control the rate-limiting and regulatory proteins in signaling pathways, remove mutated or damaged proteins, and to supply amino acids from muscle proteins for protein synthesis and gluconeogenesis (Price and Mitch 1998). There are four intracellular pathways utilized by eukaryotic cells to degrade proteins including the ATP-dependent ubiquitin-proteasome system, calcium-dependent protease, the lysosomal acid-activated protease, and the ATPindependent caspase pathways.…”

Section: Protein Degradation Proteolysis and Pro-catabolic Potentiamentioning

confidence: 99%

“…This process is repeated until several ubiquitin proteins are attached in a linear chain targeting the protein for degradation in the proteasome 26S. When targeted proteins meet the proteasome, they are unfolded and fed into the proteasome core where combinations of peptide sequence are recognized and hydrolyzed (Price and Mitch 1998). Calciumdependent protein degradation has been shown to depend on the activity of a family of cysteine proteases called calpains (Costelli, Reffo et al 2005).…”

Section: Atp and Calcium-dependent Proteolytic Processesmentioning

confidence: 99%

“…Muscle specific ubiquitin E3 ligases atrogin-1/MAFbx, muscle RING finger protein 1 (MuRF1), ubiquitin-conjugating enzyme E2 (14 kDa), and the C3, C5, and C9 proteasome subunits are important 'atrogenes' in the regulation of muscle mass and typically measured as indicators of muscle proteolytic capacity (Zheng, Ohkawa et al;Wing and Bedard 1996;Bailey, Wang et al 1999;Menconi, Fareed et al 2007). Atrogene mRNAs are typically increased with insulin deficiency or resistance in conditions of muscle wasting and decreased or degraded with insulin and IGF-1 signaling (Wing and Bedard 1996;Price and Mitch 1998). Atrogin-1 and MuRF1 mRNA levels are common indicators of myofibrillar degradation because atrogin-1 targets eukaryotic initiation factor 3 subunit 5 that induces expression of muscle specific proteins and hypertrophy, and MuRF1 targets myosin in muscle (Tisdale).…”

Section: Atrophy In T1dmmentioning

confidence: 99%

See 1 more Smart Citation

Type I Diabetes and the Role of Inflammatory-Related Cellular Signaling

Jesse¹,

Andrew²,

Myung³

et al. 2011

Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy

View full text Add to dashboard Cite

Mechanisms stimulating protein degradation to cause muscle atrophy

Cited by 28 publications

References 34 publications

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Type I Diabetes and the Role of Inflammatory-Related Cellular Signaling

Contact Info

Product

Resources

About

Mechanisms stimulating protein degradation to cause muscle atrophy

Cited by 28 publications

References 34 publications

Cachexia in the non‐obese diabetic mouse is associated with CD4+ T‐cell lymphopenia

Cachexia in the non‐obese diabetic mouse is associated with CD4+ T‐cell lymphopenia

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Type I Diabetes and the Role of Inflammatory-Related Cellular Signaling

Contact Info

Product

Resources

About

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia