S-nitrosylation of transglutaminase 2 impairs fatty acid-stimulated contraction in hypertensive cardiomyocytes

Abstract

Heart disease: A key enzyme for healthy contraction Enhancing activity of an enzyme that promotes healthy heart contraction could benefit patients at risk of serious heart conditions. Chronic high blood pressure can cause excessive thickening of heart muscle tissue, reducing the heart’s ability to contract correctly and leading to heart failure. A healthy heart fuels itself by oxidizing fatty acids to trigger production of the key energy transfer molecule ATP. Yin Hua Zhang and In-Gyu Kim at Seoul National University College of Medicine, Korea and co-workers have highlighted how S-nitrosylation, addition of nitric oxide, affects transglutaminase 2 (TG2), an enzyme that promotes ATP production. Experiments on rats and mice showed that fatty acids activate TG2, increasing ATP production and maintaining contractibility in healthy hearts. However, in pressure-overloaded hearts, TG2 activity is inhibited by S-nitrosylation, which stops heart muscle cells contracting properly.