title: Catalase protects cardiomyocytes via its inhibition of nitric oxide synthesis.
abstract: 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-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) 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-kappaB-binding affinity. However, the NO synthase activity is abolished by the addition of catalase, suggesting that H(2)O(2) is involved in NO synthesis in a posttranslation state. The catalase-induced inhibition of NO was partially but significantly reversed by H(4)B, an important cofactor of NO synthesis. Treatment of myocytes with IL-1beta, TNF-alpha, and IFN-gamma 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 H(4)B in a concentration-dependent manner. The treatment of H(4)B 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 H(4)B by the release of ROS.
authors.affiliation: Department of Dental Pharmacology and Wonkwang Biomaterial Implant Research Institute, School of Dentistry, Wonkwang University, Chonbuk 570-749, Republic of Korea.
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
authors.forename: Ki-Chan
authors.initials: KC
authors.lastname: Ha
authors.forename: Do-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Gi-Seup
authors.initials: GS
authors.lastname: Cheung
authors.forename: Yong-Geun
authors.initials: YG
authors.lastname: Kwak
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000633:toxicity*; D006352:Heart Ventricles / Q000166:cytology; D050832:Interferon-Stimulated Gene Factor 3 / Q000633:toxicity; D007375:Interleukin-1 / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D016207:Cytokines; D050832:Interferon-Stimulated Gene Factor 3; D007375:Interleukin-1; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C079868:gamma interferon activation factor; D030421:Peroxynitrous Acid; D001708:Biopterins; D009569:Nitric Oxide; D002374:Catalase; C003402:sapropterin