Catalase protects cardiomyocytes via its inhibition of nitric oxide synthesis

Nitric oxide (NO) has been reported to play an important role as an effector molecule in cytokine signal transduction in cardiomyocytes. A treatment of neonatal rat ventricular cardiomyocytes with interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) induces apoptosis via an NO-dependent pathway. However, cardiomyocytes were more resistant to NO-dependent cell death in the presence of catalase, while producing inducible nitric oxide synthase. This paper reports that catalase stimulates the NF-κB-binding affinity. However, the NO synthase activity is abolished by the addition of catalase, suggesting that H₂O₂ is involved in NO synthesis in a posttranslation state. The catalase-induced inhibition of NO was partially but significantly reversed by H₄B, an important cofactor of NO synthesis. Treatment of myocytes with IL-1β, TNF-α, and IFN-γ induced a significant increase in the formation of peroxynitrite, and a pretreatment with catalase was found to quench the production of peroxynitrite. This paper shows that the catalase activity was significantly down-regulated by H₄B in a concentration-dependent manner. The treatment of H₄B induced reactive oxygen species (ROS) release in cardiac cell system. These results suggest that catalase interferes with NO and peroxynitrite production as well as with the related apoptosis of cardiomyocytes. This study also shows that the catalase-induced inhibition of NO release may be reversed by H₄B by the release of ROS.