Wink D A, Cook J A, Pacelli R, DeGraff W, Gamson J, Liebmann J, Krishna M C, Mitchell J B
Tumor Biology Section, National Cancer Institute, Bethesda, Maryland, 20892, USA.
Arch Biochem Biophys. 1996 Jul 15;331(2):241-8. doi: 10.1006/abbi.1996.0304.
The role that nitric oxide (NO) plays in various degenerative and disease states has remained a mystery since its discovery as a biological messenger, prompting the question, "NO, friend or foe?" Some reports have suggested that NO is cytotoxic, and yet others have shown that it possesses protective properties against reactive oxygen species (ROS). Many studies have used various NO donor complexes arriving at seemingly different conclusions. This report will address the effects of various NO donor compounds on ROS-mediated toxicity. Consistent with our previous study, the NO donor compound, DEA/NO ((C2H5)2N[N(O)NO]-Na+), afforded protection against hydrogen peroxide-mediated cytotoxicity in V79 Chinese hamster lung fibroblasts at concentrations as low as 10 microM DEA/NO. Furthermore, a survey of other NO donor complexes revealed that some either protected or potentiated hydrogen peroxide-mediated cytotoxicity. 3-Morpholinosynodiomine.HCl (SIN-1) and sodium nitroprusside (SNP) enhanced hydrogen peroxide-mediated cytotoxicity, while S-nitrosoglutathione (GSNO), and S-nitroso-N-acetylpenicillamine (SNAP) afforded protection. Electrochemical detection of NO in cell culture medium revealed that neither 1000 microM SIN-1 nor SNP yielded appreciable NO concentrations (<0.3 microM). In contrast, DEA/NO, SNAP, and GSNO yielded fluxes of NO >1.0 microM. Thus, a direct correlation between inhibition of hydrogen peroxide cytotoxicity and NO production was observed: agents that release NO during hydrogen peroxide treatment afford significant protection, whereas agents that do not release NO do not protect. Similar results were observed for NO donors studied when hypoxanthinesolidusxanthine oxidase was used as the source for ROS, although the S-nitrosothiol agents were much less protective. These results demonstrate that NO possesses properties which protect against ROS toxicity and demonstrate how the use of different NO donor compounds can lead to different conclusions about the role that NO can play in the cytotoxicity of ROS.
自一氧化氮（NO）作为生物信使被发现以来，它在各种退行性疾病和疾病状态中所起的作用一直是个谜，这引发了一个问题：“NO，是友还是敌？”一些报告表明NO具有细胞毒性，而另一些报告则显示它对活性氧（ROS）具有保护特性。许多研究使用了各种NO供体复合物，得出了看似不同的结论。本报告将探讨各种NO供体化合物对ROS介导的毒性的影响。与我们之前的研究一致，NO供体化合物DEA/NO（（C2H5）2N[N（O）NO]-Na+）在低至10 microM DEA/NO的浓度下，对V79中国仓鼠肺成纤维细胞中过氧化氢介导的细胞毒性具有保护作用。此外，对其他NO供体复合物的研究表明，有些复合物要么具有保护作用，要么增强了过氧化氢介导的细胞毒性。3-吗啉代辛二胺盐酸盐（SIN-1）和硝普钠（SNP）增强了过氧化氢介导的细胞毒性，而S-亚硝基谷胱甘肽（GSNO）和S-亚硝基-N-乙酰青霉胺（SNAP）则具有保护作用。对细胞培养基中NO的电化学检测表明，1000 microM的SIN-1和SNP都没有产生可观的NO浓度（<0.3 microM）。相比之下，DEA/NO、SNAP和GSNO产生的NO通量>1.0 microM。因此，观察到过氧化氢细胞毒性的抑制与NO产生之间存在直接相关性：在过氧化氢处理过程中释放NO的试剂具有显著的保护作用，而不释放NO的试剂则没有保护作用。当使用次黄嘌呤/黄嘌呤氧化酶作为ROS来源时，对所研究的NO供体也观察到了类似的结果，尽管S-亚硝基硫醇试剂的保护作用要小得多。这些结果表明，NO具有抵御ROS毒性的特性，并证明了使用不同的NO供体化合物如何导致关于NO在ROS细胞毒性中所起作用的不同结论。
