title: Des-aspartate-angiotensin I attenuates ICAM-1 formation in hydrogen peroxide-treated L6 skeletal muscle cells and soleus muscle of mice subjected to eccentric exercise.
abstract: L6 skeletal muscle cells overexpressed ICAM-1 when treated with H2O2. Maximum effect was observed at 200 μM H2O2. Des-aspartate-angiotensin I (DAA-I) concentration-dependently attenuated the overexpression. Maximum attenuation occurred at 10(-10) M DAA-I. H2O2 activated NFκB and its translocation into the nucleus of L6 muscle cells suggesting that NFκB mediates the H2O2-induced overexpression of ICAM-1. DAA-I inhibited the activation and translocation of NFκB. H2O2 is a major oxidant formed during skeletal muscle contraction and is implicated in oxidative stress and skeletal muscle damage in excessive unaccustomed exercise. The data show that DAA-I has antioxidant action, and its action was further investigated in the soleus muscle of mice subjected to 240 min of eccentric exercise on a rodent treadmill. The eccentric exercise induced superoxide formation and overexpression of ICAM-1 in the soleus muscle of the mice at 3 days post exercise. DAA-I (0.2 nmole/kg/day) administered orally on day 1 (pre-exercise) and 2 days post-exercise attenuated both the ROS formation and ICAM-1 overexpression. Earlier studies show that DAA-I acts as an agonist on the angiotensin AT1 receptor and elicits responses opposing those of angiotensin II. The present and earlier findings support the recent suggestion that angiotensin II is involved in skeletal muscle damage, and curtailment of its actions via ACE inhibitors and losartan protects and improves skeletal muscle damage. These findings open up new avenues for treatment and management of skeletal muscle damage via the interventions of the renin angiotensin system.
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address: phcsimmk@nus.edu.sg.
authors: Meng-Kwoon
authors: MK
authors: Sim
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors: Yong-Chiat
authors: YC
authors: Wong
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors: Xiao-Guang
authors: XG
authors: Xu
authors: Agent Diagnostics and Therapeutics Laboratory, Defense & Environmental Research Institute, DSO National Laboratories, 11 Stockpark Road, 117605, Singapore.
authors: Weng-Keong
authors: WK
authors: Loke
mesh_terms: D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology*; D010805:Physical Conditioning, Animal; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: C090509:Icam1 protein, mouse; D016877:Oxidants; C529402:des-aspartate-angiotensin I; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D000803:Angiotensin I; D006861:Hydrogen Peroxide
keywords: Des-aspartate-angiotensin I; Eccentric exercise; ICAM-1; Skeletal muscle damage; Soleus muscle; Superoxide