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Cirrhosis was induced by bile duct ligation (BDL) in male adult Sprague-Dawley rats. mRNA and protein levels of various targets were determined by RT-PCR and Western blotting, respectively. The proteolytic rate was measured ex vivo using isolated muscles. Compared with sham-operated controls, BDL rats had an increased degradation rate of muscle proteins and enhanced gene expression of ubiquitin, 14-kDa ubiquitin carrier protein E2, and the proteasome subunits C2 and C8 ( P &lt; 0.01). The muscle protein levels of free ubiquitin and conjugated ubiquitin levels were also elevated ( P &lt; 0.01). However, there was no difference between the two groups with regard to cathepsin and calpain mRNA levels. Cirrhotic muscle TNF-\u03b1 levels were increased and correlated positively with free and conjugated ubiquitin ( P &lt; 0.01). We conclude that the ubiquitin-proteasome system is involved in muscle wasting of rats with BDL-induced cirrhosis. TNF-\u03b1 might play a role in mediating activation of this proteolytic pathway, probably through a local mechanism.<\/jats:p>","DOI":"10.1152\/ajpendo.00186.2004","type":"journal-article","created":{"date-parts":[[2004,11,3]],"date-time":"2004-11-03T03:18:12Z","timestamp":1099451892000},"page":"E493-E501","source":"Crossref","is-referenced-by-count":53,"title":["Activation of ubiquitin-proteasome pathway is involved in skeletal muscle wasting in a rat model with biliary cirrhosis: potential role of TNF-\u03b1"],"prefix":"10.1152","volume":"288","author":[{"given":"Shih-Yi","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Yauh","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Jang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne Huey-Herng","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1097\/00075197-200101000-00009"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704103361506"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1159\/000177817"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.5.R1518"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000069728.49939.E4"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1042\/bj2120649"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1993.01420140077012"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"CombarbetL, Tilignac T, Claustre A, Voisin L, Taillandier D, Obled C, Tanaka K, and Attaix D.Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin-proteasome-dependent proteolysis in cancer and septic rats.Biochem J361: 185\u2013192, 2002.","DOI":"10.1042\/bj3610185"},{"key":"R9","unstructured":"CookEB, Gove CD, Panos MZ, Williams R, and Preedy VR.Skeletal muscle protease activities are unaltered in cirrhotic rats but altered in response to ethanol and acetaldehyde in vitro.Alcohol Alcohol30: 203\u2013209, 1995."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116897"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90418-9"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110416"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)65308-7"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00054.2002"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81341-V"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1754"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90147-7"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80009-3"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.260.5.E727"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/44.3.362"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"GreenJH, Bramley PN, and Losowsky MS.Are patients with primary biliary cirrhosis hypermetabolic? 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