Protein nitration is associated with increased proteolysis in skeletal muscle of bile duct ligation-induced cirrhotic rats.
Cirrhosis is characterized by skeletal muscle wasting. In this study, the effects of nitric oxide production on skeletal muscle protein nitration and degradation in cirrhosis were investigated. Cirrhosis was induced by bile duct ligation (BDL) in Sprague-Dawley rats for 4 weeks. The BDL-induced cirrhotic rats and sham-operated rats were then injected daily with either saline or N(G)-l-nitro-arginine methyl ester (l-NAME) for 7 days from week 4 to week 5, after which nitrite/nitrate, glutathione reduction, as well as protein nitration, ubiquitination, and degradation were assessed in skeletal muscle. Elevated muscular nitrite/nitrate concentrations, protein nitration, total ubiquitin conjugates, and degradation fragments of myosin heavy chain as well as diminished glutathione reduction levels were observed in BDL-induced cirrhotic rats as compared with controls. Administration of l-NAME for 1 week led to reduction of nitrite/nitrate levels; protein nitration was also decreased in the skeletal muscle. In addition, ubiquitination of muscular proteins and degradation of myosin heavy chain were significantly diminished after treatment of l-NAME. In conclusion, nitrosative stress occurred in the skeletal muscle of BDL-induced cirrhotic rats and may lead to increased proteolysis of muscle-specific structural proteins.
Wang
Ya-Yu
YY
Division of Family Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
Lin
Shih-Yi
SY
Chuang
Yu-Han
YH
Mao
Chia-Hung
CH
Tung
Kwong-Chung
KC
Sheu
Wayne Huey-Herng
WH
D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D005978:Glutathione / Q000032:analysis; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054875:Ubiquitination
D009124:Muscle Proteins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D018995:Myosin Heavy Chains; D005978:Glutathione