Nitric oxide protects macrophages from hydrogen peroxide-induced apoptosis by inducing the formation of catalase.
We investigated the cytoprotective effect of NO on H2O2-induced cell death in mouse macrophage-like cell line RAW264. H2O2-treated cells showed apoptotic features, such as activation of caspase-9 and caspase-3, nuclear fragmentation, and DNA fragmentation. These apoptotic features were significantly inhibited by pretreatment for 24 h with NO donors, sodium nitroprusside and 1-hydroxy-2-oxo-3,3-bis-(2-aminoethyl)-1-triazene, at a low nontoxic concentration. The cytoprotective effect of NO was abrogated by the catalase inhibitor 3-amino-1,2,4-triazole but was not affected by a glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine. NO donors increased the level of catalase and its activity in a concentration-dependent manner. Cycloheximide, a protein synthesis inhibitor, inhibited both the NO-induced increase in the catalase level and the cytoprotective effect of NO. These results indicate that NO at a low concentration protects macrophages from H2O2-induced apoptosis by inducing the production of catalase.
Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan. yoshioka@pharm.setsunan.ac.jp
Yasuhiro
Y
Yoshioka
Tatsuya
T
Kitao
Takashi
T
Kishino
Akiko
A
Yamamuro
Sadaaki
S
Maeda
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000096:biosynthesis*; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D015398:Signal Transduction
C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D006152:Cyclic GMP