Abstract
It is now well known that oxidative stress promotes lipid peroxidation, protein oxidation, activation of proteases, fragmentation of DNA and alteration in gene expression for producing myocardial cell damage, whereas its actions for the induction of fibrosis, necrosis and apoptosis are considered to result in the loss of cardiomyocytes in different types of heart disease. The present article is focused on the discussion concerning the generation and implications of oxidative stress from various sources such as defective mitochondrial electron transport and enzymatic reactions mainly due to the activation of NADPH oxidase, nitric oxide synthase and monoamine oxidase in diseased myocardium. Oxidative stress has been reported to promote excessive entry of Ca(2+) due to increased permeability of the sarcolemmal membrane as well as depressions of Na(+)-K(+) ATPase and Na(+)-Ca(2+) exchange systems, which are considered to increase the intracellular of Ca(2+). In addition, marked changes in the ryanodine receptors and Ca(2+)-pump ATPase have been shown to cause Ca(2+)-release and depress Ca(2+) accumulation in the sarcoplasmic reticulum as a consequence of oxidative stress. Such alterations in sarcolemma and sarcoplasmic reticulum are considered to cause Ca(2+)-handling abnormalities, which are associated with mitochondrial Ca(2+)-overload and loss of myofibrillar Ca(2+)-sensitivity due to oxidative stress. Information regarding the direct effects of different oxyradicals and oxidants on subcellular organelles has also been outlined to show the mechanisms by which oxidative stress may induce Ca(2+)-handling abnormalities. These observations support the view that oxidative stress plays an important role in the genesis of subcellular defects and cardiac dysfunction in heart disease.