Strategies for suppressing muscle atrophy in chronic kidney disease: mechanisms activating distinct proteolytic systems.

@article{citeulike:2961616, abstract = {Loss of protein and lean body mass occurs commonly in patients with chronic kidney disease (CKD). CKD or conditions associated with CKD will stimulate muscle loss, but the cellular mechanisms by which these conditions cause muscle atrophy are largely undefined. In animal models of uremia and other catabolic conditions or in peritoneal dialysis patients, there is evidence that the ubiquitin-proteasome proteolytic system is activated to degrade actomyosin and myofibrillar proteins in muscle. Before the ubiquitin system can degrade muscle proteins, however, an initial cleavage of actomyosin and myofibrils must occur. Caspase-3 performs this initial cleavage of actomyosin and leaves a footprint of its activity, accumulation of a 14-kDa actin fragment in muscle. A critical step in stimulating the ubiquitin-proteasome system in muscle was recently discovered, the activation of a specific E3 ubiquitin-conjugating enzyme, atrogin-1. Both caspase-3 and the ubiquitin system, including atrogin-1, are activated when insulin signaling is impaired, and specifically when phosphatidylinositol 3 kinase activity is suppressed. Strategies that prevent a decrease in phosphatidylinositol 3 kinase activity or inhibit caspase-3 activity could lead to treatments that prevent muscle wasting in CKD patients.}, address = {Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA. wmitch@utmb.edu <wmitch@utmb.edu>}, author = {Mitch, W. E. and Hu, Z. and Lee, S. W. and Du, J. }, citeulike-article-id = {2961616}, issn = {1532-8503}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, keywords = {cachexia, ckd}, month = {January}, number = {1}, pages = {23--27}, posted-at = {2008-07-04 02:57:18}, priority = {2}, title = {Strategies for suppressing muscle atrophy in chronic kidney disease: mechanisms activating distinct proteolytic systems.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/15648002}, volume = {15}, year = {2005} }

TY - JOUR ID - citeulike:2961616 L3 - citeulike-article-id:2961616 TI - Strategies for suppressing muscle atrophy in chronic kidney disease: mechanisms activating distinct proteolytic systems. JF - Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation VL - 15 IS - 1 SP - 23 EP - 27 AD - Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA. wmitch@utmb.edu <wmitch@utmb.edu> SN - 1532-8503 N2 - Loss of protein and lean body mass occurs commonly in patients with chronic kidney disease (CKD). CKD or conditions associated with CKD will stimulate muscle loss, but the cellular mechanisms by which these conditions cause muscle atrophy are largely undefined. In animal models of uremia and other catabolic conditions or in peritoneal dialysis patients, there is evidence that the ubiquitin-proteasome proteolytic system is activated to degrade actomyosin and myofibrillar proteins in muscle. Before the ubiquitin system can degrade muscle proteins, however, an initial cleavage of actomyosin and myofibrils must occur. Caspase-3 performs this initial cleavage of actomyosin and leaves a footprint of its activity, accumulation of a 14-kDa actin fragment in muscle. A critical step in stimulating the ubiquitin-proteasome system in muscle was recently discovered, the activation of a specific E3 ubiquitin-conjugating enzyme, atrogin-1. Both caspase-3 and the ubiquitin system, including atrogin-1, are activated when insulin signaling is impaired, and specifically when phosphatidylinositol 3 kinase activity is suppressed. Strategies that prevent a decrease in phosphatidylinositol 3 kinase activity or inhibit caspase-3 activity could lead to treatments that prevent muscle wasting in CKD patients. KW - cachexia KW - ckd AU - Mitch, WE AU - Hu, Z AU - Lee, SW AU - Du, J PY - 2005/01// UR - http://view.ncbi.nlm.nih.gov/pubmed/15648002 ER -