Abstract
The pathophysiological consequences of kidney failure and other catabolic conditions such as diabetes, burn injury, cancer, sepsis, muscle denervation and starvation, include loss of protein stores. This chapter will describe the impressive concordance between studies performed with cultured muscle cells and studies involving experimental animals and patients suggests that there is strong evolutionary pressure to maintain these “stress”-related responses. Understanding the mechanisms leading to activation of transcription could lead to improved methods of preventing the loss of muscle protein.
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Selected References
Alvestrand A. Carbohydrate and insulin metabolism in renal failure. Kidney Int Suppl 1997;62:S48–S52.
Bailey JL, England BK, Long RC Jr, Weissman J, Mitch WE. Experimental acidemia and muscle cell pH in chronic acidosis and renal failure. Am J Physiol 1995;269:C706–C712.
Bailey JL, Wang X, England BK, Price SR, Ding X, Mitch WE. The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent, ubiquitin-proteasome pathway. J Clin Invest 1996;97:1447–1453.
Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001;294:1704–1708.
Cecchin F, Ittoop O, Sinha MK, Caro JF. Insulin resistance in uremia: insulin receptor kinase activity in liver and muscle from chronic uremic rats. Am J Physiol 1988;254:E394–E401.
DeFronzo RA, Alvestrand A, Smith D, Hendler R. Insulin resistance in uremia. J Clin Invest 1981;67:563–568.
Du J, Mitch WE, Wang X, Price SR. Glucocorticoids induce proteasome C3 subunit expression in L6 muscle cells by opposing the suppression of its transcription by NF-κB. J Biol Chem 2000;275:19,661–19,666.
Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002;82(2): 373–428.
Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 2001;98(25): 14,440–14,445.
Hasselgren PO. Glucocorticoids and muscle catabolism. Curr Opin Clin Nutr Metab Care 1999;2:201–205.
Jagoe RT, Goldberg AL. What do we really know about the ubiquitinproteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care 2001;4(3):183–190.
Jagoe RT, Lecker SH, Gomes M, Goldberg AL. Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. Faseb J 2002;16(13):1697–1712.
Karin M, Chang L. AP-1-glucocorticoid receptor crosstalk taken to a higher level. J Endocrinol 2001;169(3):447–451.
Marinovic AC, Zheng B, Mitch WE, Price SR. Ubiquitin (UbC) expression in muscle cells is increased by glucocorticoids through a mechanism involving Sp1 and MEK1. J Biol Chem 2002;277(19):16,673–16,681.
May RC, Kelly RA, Mitch WE. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism. J Clin Invest 1986;77:614–621.
McKay LI, Cidlowski JA. Cross-talk between nuclear factor-κB and steroid hormone receptors: mechanisms of mutual antagonism. Mol Endocrinol 1998;12(1):45–56.
Mehrotra R, Kopple JD. Nutritional management of maintenance dialysis patients: why aren’t we doing better? Annu Rev Nutr 2001;21:343–379.
Mitch WE, Bailey JL, Wang X, Jurkovitz C, Newby D, Price SR. Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. Am J Physiol 1999;276:C1132–C1138.
Mitch WE, Goldberg AL. Mechanisms of muscle wasting: The role of the ubiquitin-proteasome pathway. N Engl J Med 1996; 335(25): 1897–1905.
Mitch WE, Price SR. Mechanisms activated by kidney disease and the loss of muscle mass. Am J Kidney Dis 2001;38(6): 1337–1342.
Nenoi M, Mita K, Ichimura S, et al. Hetergeneous structure of the polyubiquitin gene UbC of Hela S3 cells. Gene 1996;175:179–185.
Penner CG, Gang G, Wray C, Fischer JE, Hasselgren PO. The transcription factors NF-kappaB and AP-1 are differentially regulated in skeletal muscle during sepsis. Biochem Biophys Res Commun 2001;281(5): 1331–1336.
Pickering WP, Price SR, Bircher G, Marinovic AC, Mitch WE, Walls J. Nutrition in CAPD: serum bicarbonate and the ubiquitin-proteasome system in muscle. Kidney Int 2002;61(4):1286–1292.
Price SR, Bailey JL, Wang X, et al. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 1996;98:1703–1708.
Samson SL, Wong NC. Role of Sp1 in insulin regulation of gene expression. J Mol Endocrinol 2002;29(3):265–279.
Solomon V, Goldberg AL. Importance of the ATP-ubiquitin-proteasome pathway in the degradation of soluble and myofibrillar proteins in rabbit muscle extracts. J Biol Chem 1996;271(43):26,690–26,697.
Varshavsky A. The N-end rule and regulation of apoptosis. Nat Cell Biol 2003;5(5):373–376.
Wiborg O, Pedersen MS, Wind A, Berglund LE, Marcker KA, Vuust J. The human ubiquitin multigene family: some genes contain multiple directly repeated ubiquitin coding sequences. Embo J 1985;4: 755–759.
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Price, S.R., Mitch, W.E. (2006). Loss of Lean Body Mass in Uremia. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_64
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DOI: https://doi.org/10.1007/978-1-59259-963-9_64
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