Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production
Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production
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DOI：
10.1211/0022357055731
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发表时间：
2005-04-01
影响因子：
3.3
通讯作者：
Chung, HY
中科院分区：
文献类型：
--
作者：
Kim, AR;Cho, JY;Chung, HY
过氧亚硝酸盐(ONOO-)是一种由一氧化氮(中心点NO)和超氧阴离子自由基(中心点O-2(-))反应形成的强有力的细胞毒性氧化剂，由于氧化和硝化过程，在细胞环境中可能会迅速致死。在本研究中，对苯二酚在小鼠巨噬细胞RAW264.7细胞中表现出较强的ONOO清除活性和抑制NO生成的作用。与其他活性物种如中心点O-2(-)和中心点NO相比，对苯二酚对ONOO诱导的二氢罗丹明123氧化具有较强的清除作用，且呈剂量依赖关系。对苯二酚还能降低ONOO诱导的谷胱甘肽还原酶的硝基酪氨酸水平，从而保护该酶免受ONOO的损伤。此外，在脂多糖激活的RAW264.7细胞中，氢醌通过抑制诱导型NO合成酶的表达来抑制NO的产生，这是ONOO形成的细胞途径。对苯二酚的抑制作用可能是通过阻断脂多糖诱导的信号转导，如核因子-kappaB和细胞外信号相关酶1和2的激活而实现的。这些结果表明，对苯二酚可能有效地调节ONOO的反应性，因此可能是一种有用的抗ONOO介导性疾病的药物。
Peroxynitrite (ONOO-), a potent cytotoxic oxidant formed by the reaction of nitric oxide (center dot NO) and superoxide radical (center dot O-2(-)), may be rapidly lethal in a cellular milieu due to oxidization and nitration processes. In the present study, hydroquinone displayed strong ONOO- scavenging activity and inhibitory effect on NO production in murine macrophage RAW264.7 cells. Hydroquinone strongly scavenged ONOO- induced dihydrorhodamine 123 oxidation in a dose-dependent manner compared with other reactive species such as center dot O-2(-) and center dot NO. Hydroquinone also decreased levels of ONOO induced nitrotyrosine of glutathione reductase and consequently prevented the enzyme from ONOO- induced damage. Furthermore, hydroquinone suppressed NO production, a cellular pathway for ONOO- formation, in lipopolysaccharide-activated RAW264.7 cells via inhibition of inducible NO synthase expression. The inhibitory effect by hydroquinone seems to be mediated by interruption of lipopolysaccharide-induced signalling such as activation of nuclear factor-kappa B and extracellular signal-related kinases 1 and 2. The results suggest that hydroquinone may potently modulate reactivity of ONOO- and may therefore be a useful agent against ONOO- mediated diseases.