Effects of reactive oxygen and nitrogen species on actomyosin and their implications for muscle contractility

Experimental evidence accumulated during recent years is pointing out that numerous pathological conditions in skeletal and cardiac muscle are associated with an oxidative stress-induced muscle injury. Additionally, it has been postulated that several oxidants can directly alter contractile function by oxidative modification of the myofibril proteins – Correspondence/Reprint request: Dr. Teresa Tiago, Faculdade de Ciencias e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal. E-mail: ttiago@ualg.pt Teresa Tiago et al. 2 actin and myosin. Peroxynitrite (ONOO-), a potent biological oxidizing agent formed in the nearly instantaneous reaction of nitric oxide with superoxide anion, is increasingly recognized as playing a major role in the skeletal and cardiac muscle dysfunction. This is supported by detection of 3-nitrotyrosine, a protein modification produced by the reaction of peroxynitrite with tyrosine, on skeletal and cardiac muscle proteins during aging or in diseases associated with myocardial inflammation or ischemia/reperfusion insults. Although some studies point to a correlation of protein nitration with functional and structural modifications, the mechanism by which peroxynitrite may impair muscle contractility remains far from being elucidated. In the present review we address the role of reactive oxygen and nitrogen species on the structural and functional impairment of actomyosin ATPase activity and their implications for muscle contraction with particular emphasis on the oxidative modifications promoted by peroxynitrite on actin and myosin.