iNOS inhibitor, L-NIL, reverses burn-induced glycogen synthase kinase-3β activation in skeletal muscle of rats

• Published in: Metabolism, clinical and experimental clinical and experimental, 2013-03, Vol.62 (3), p.341-346
• Main Authors: Kaneki, Masao, Fukushima, Yuji, Shinozaki, Shohei, Fukaya, Makiko, Habiro, Mayu, Shimizu, Nobuyuki, Chang, Kyungho, Yasuhara, Shingo, Martyn, J.A. Jeevendra
• Format: Article
• Language: English
• Subjects: Akt/PKB; Animals; Biological and medical sciences; Burns; Burns - enzymology; Burns - metabolism; Endocrinology & Metabolism; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glycogen Synthase - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Lysine - analogs & derivatives; Lysine - pharmacology; Male; Medical sciences; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Muscle, Skeletal - injuries; Muscle, Skeletal - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Phosphorylation; Random Allocation; Rats; Rats, Sprague-Dawley; Traumas. Diseases due to physical agents; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2012.08.010

Abstract Objectives Recent studies suggest that activation of glycogen synthase kinase (GSK)-3β may be involved in burn injury-induced metabolic derangements and protein breakdown in skeletal muscle. However, the mechanism for GSK-3β activation after burn injury is unknown. To investigate the role of inducible nitric oxide synthase (iNOS) in this scenario, a major mediator of inflammation, we examined the effects of a specific inhibitor for iNOS, L-NIL, on GSK-3β activity in skeletal muscle of burned rats. Materials/Methods Full-thickness third degree burn injury comprising 40% of total body surface area was produced under anesthesia in male Sprague–Dawley rats (160–190 g) by immersing the back of the trunk for 15 s and the abdomen for 8 s in 80 °C water. Burned and sham-burned rats were treated with L-NIL (60 mg/kg BW, b.i.d., IP) or phosphate-buffered saline for three days. GSK-3β activity in skeletal muscle was evaluated by immune complex kinase assay, and by phosphorylation status of GSK-3β and its endogenous substrate, glycogen synthase. Results GSK-3β activity was increased in a time-dependent manner in skeletal muscle after burn injury, concomitant with the induction of iNOS expression. iNOS inhibitor, L-NIL, reverted the elevated GSK-3β activity in skeletal muscle of burned rats, although L-NIL did not alter GSK-3β activity in sham-burned rats. Conclusions Our results clearly indicate that iNOS plays an important role in burn injury-induced GSK-3β activation in skeletal muscle. These findings suggest that iNOS may contribute to burn injury-induced metabolic derangements, in part, by activating GSK-3β.