Cellular signals activating muscle proteolysis in chronic kidney disease: A two-stage process

@article{citeulike:2940986, abstract = {Muscle atrophy is a prominent feature of catabolic conditions and in animal models of these conditions there is accelerated muscle proteolysis that is dependent on the ubiquitin-proteasome system. However, ubiquitin system cannot degrade actomyosin or myofibrils even though it rapidly degrades actin or myosin. We identified caspase-3 as the initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils. In rodent models of catabolic conditions, we find that caspase-3 is activated to cleave muscle proteins and actomyosin to fragments that are rapidly degraded by the ubiquitin system. This initial proteolytic step in muscle can be recognized because it leaves a footprint of a characteristic 14-kDa actin band. Stimulation of caspase-3 activity depends on activation of phosphatidylinositol 3-kinase. When we suppressed this enzyme in muscle cells, protein breakdown increased as did the expression of caspase-3. In addition, there was increased expression of E3-ubiquitin-conjugating enzymes that are involved in muscle proteolysis, atrogin-1/MAFbx and MuRF1. Thus, when phosphatidylinositol 3-kinase activity is low in muscle cells or rat muscle, both caspase-3 and the ubiquitin-proteasome system are stimulated to degrade protein. Additional investigations will be needed to define the cell signaling processes that activate muscle proteolysis in uremia and catabolic conditions.}, author = {Du, Jie and Hu, Zhaoyong and Mitch, William E. }, booktitle = {Muscle Wasting: From Molecular Regulation to Novel Therapies}, citeulike-article-id = {2940986}, doi = {http://dx.doi.org/10.1016/j.biocel.2005.03.012}, journal = {The International Journal of Biochemistry \& Cell Biology}, keywords = {cachexia, ckd, nutrition}, month = {October}, number = {10}, pages = {2147--2155}, posted-at = {2008-06-29 07:32:40}, priority = {2}, title = {Cellular signals activating muscle proteolysis in chronic kidney disease: A two-stage process}, url = {http://dx.doi.org/10.1016/j.biocel.2005.03.012}, volume = {37}, year = {2005} }

TY - JOUR ID - citeulike:2940986 L3 - citeulike-article-id:2940986 TI - Cellular signals activating muscle proteolysis in chronic kidney disease: A two-stage process T2 - Muscle Wasting: From Molecular Regulation to Novel Therapies JF - The International Journal of Biochemistry & Cell Biology VL - 37 IS - 10 SP - 2147 EP - 2155 N2 - Muscle atrophy is a prominent feature of catabolic conditions and in animal models of these conditions there is accelerated muscle proteolysis that is dependent on the ubiquitin-proteasome system. However, ubiquitin system cannot degrade actomyosin or myofibrils even though it rapidly degrades actin or myosin. We identified caspase-3 as the initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils. In rodent models of catabolic conditions, we find that caspase-3 is activated to cleave muscle proteins and actomyosin to fragments that are rapidly degraded by the ubiquitin system. This initial proteolytic step in muscle can be recognized because it leaves a footprint of a characteristic 14-kDa actin band. Stimulation of caspase-3 activity depends on activation of phosphatidylinositol 3-kinase. When we suppressed this enzyme in muscle cells, protein breakdown increased as did the expression of caspase-3. In addition, there was increased expression of E3-ubiquitin-conjugating enzymes that are involved in muscle proteolysis, atrogin-1/MAFbx and MuRF1. Thus, when phosphatidylinositol 3-kinase activity is low in muscle cells or rat muscle, both caspase-3 and the ubiquitin-proteasome system are stimulated to degrade protein. Additional investigations will be needed to define the cell signaling processes that activate muscle proteolysis in uremia and catabolic conditions. KW - cachexia KW - ckd KW - nutrition AU - Du, Jie AU - Hu, Zhaoyong AU - Mitch, William PY - 2005/10// UR - http://dx.doi.org/10.1016/j.biocel.2005.03.012 ER -