Brennan Lisa A, Wedgwood Stephen, Black Stephen M
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
IUBMB Life. 2002 Nov;54(5):261-5. doi: 10.1080/15216540215679.
Previously, we have demonstrated that increased superoxide generation plays a role in the nitric oxide (NO)-mediated inhibition of endothelial NO synthase (eNOS) in endothelial cells (ECs) and that the overexpression of SOD1 could reduce the inhibitory effect of NO. However, SOD1 overexpression did not completely abolish the inhibition of eNOS by NO, indicating the presence of other inhibitory mechanisms. Because superoxide can be dismutated into hydrogen peroxide (H2O2), in this study we determined whether exposure of ECs to NO resulted in increased generation of H2O2 and the potential role of H2O2 in eNOS inhibition. Our results indicated that H2O2 levels were increased in response to NO. Using adenoviral-mediated infection, we demonstrated that catalase overexpression both increased basal eNOS activity in the absence of NO and provided a significant protective effect on eNOS activity in the presence of NO. This protective effect was associated with a significant decrease in H2O2 levels in the presence of NO. In conclusion, our results indicate that increased levels of H2O2 may be involved in the inhibition of eNOS by NO and that the scavenging of H2O2 may be useful to prevent eNOS inhibition during treatments that involve inhaled NO or NO donors.
此前，我们已经证明，超氧化物生成增加在内皮细胞（ECs）中一氧化氮（NO）介导的内皮型一氧化氮合酶（eNOS）抑制过程中发挥作用，并且超氧化物歧化酶1（SOD1）的过表达可降低NO的抑制作用。然而，SOD1过表达并未完全消除NO对eNOS的抑制作用，这表明存在其他抑制机制。由于超氧化物可歧化为过氧化氢（H2O2），因此在本研究中，我们确定了ECs暴露于NO是否会导致H2O2生成增加以及H2O2在eNOS抑制中的潜在作用。我们的结果表明，H2O2水平会因NO而升高。通过腺病毒介导的感染，我们证明过氧化氢酶过表达不仅在无NO的情况下增加了基础eNOS活性，而且在有NO的情况下对eNOS活性提供了显著的保护作用。这种保护作用与有NO存在时H2O2水平的显著降低有关。总之，我们的结果表明，H2O2水平升高可能参与了NO对eNOS的抑制作用，并且清除H2O2可能有助于在涉及吸入NO或NO供体的治疗过程中防止eNOS受到抑制。
