Nitric oxide, peroxynitrite and nitroso-compounds formation by ultraviolet A (UVA) irradiated human squamous cell carcinoma: potential role of nitric oxide in cancer prognosis.
Nitric oxide, peroxynitrite and nitroso-compounds formation by ultraviolet A (UVA) irradiated human squamous cell carcinoma: potential role of nitric oxide in cancer prognosis.
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紫外线 A (UVA) 照射人鳞状细胞癌形成一氧化氮、过氧亚硝酸盐和亚硝基化合物：一氧化氮在癌症预后中的潜在作用。
DOI：
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发表时间：
1995
影响因子：
2
通讯作者：
G. Deliconstantinos
中科院分区：
文献类型：
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作者：
V. Villiotou;G. Deliconstantinos
紫外线A（UVA）照射人鳞状细胞癌（SCC-13）释放氮氧化物，即一氧化氮（NO）、过氧亚硝酸盐（ONOO-）、亚硝基化合物、氨（NH3）和由L-精氨酸形成的羟胺（H2 NOH）。这些氮氧化物的形成和/或释放的时间和浓度依赖性刺激UVA和N-单甲基-L-精氨酸（L-NMMA），一种化合物，抑制NO合酶活性的减少。UVA照射SCC-13细胞导致可溶性鸟苷酸环化酶（sGC）的同时增加，L-NMMA抑制sGC。由二丁酰cGMP和3-异丁基-1-甲基-黄嘌呤（IBMX）引起的NO和ONOO-产生的增加代表了另外的正反馈机制，其可以用于在UVA辐射后维持NO和ONOO-释放延长的时间段。利用体外化学模型系统，证明了在生理pH下，羟基自由基（.OH）将NH3氧化为NO在化学上是可行的。UVA照射的SCC-13细胞诱导鲁米诺增强的化学发光信号，在1分钟内达到峰值。依布硒对该信号的调制与鲁米诺-超氧化物（O2-）复合物的分解相对应的速率决定步骤一致。UVA照射SCC-13细胞后，MDA含量增加，细胞膜流动性降低。在UVA照射的SCC-13细胞中测试的去铁胺显示出MDA产生的浓度依赖性降低，随后膜流动性恢复到正常水平。此外，它表明，鳞状细胞癌具有较高的NO合酶和sGC活性相比，正常角质形成细胞。这种NO产生的增加可能与鳞状细胞癌的不良预后直接相关。
Ultraviolet A (UVA) irradiated human squamous cell carcinoma (SCC-13) releases nitrogen oxides, i.e. nitric oxide (NO), peroxynitrite (ONOO-), nitrosocompounds, ammonia (NH3) and hydroxylamine (H2NOH) formed from L-arginine. Formation and/or release of these nitrogen oxides was time and concentration-dependently stimulated by UVA and decreased by N-monomethyl-L-arginine (L-NMMA), a compound that inhibits NO synthase activity. UVA irradiation of SCC-13 cells resulted in concomitant increase in soluble guanylate cyclase (sGC) which was inhibited by L-NMMA. The increased NO and ONOO- production evoked by dibutyryl cGMP and 3-isobutyl-l-methyl-xanthine (IBMX) represents an additional positive feedback mechanism that could serve to maintain NO and ONOO- release for extended periods following UVA radiation. Using an in vitro chemical model system, it was demonstrated that oxidation of NH3 to NO by hydroxyl radical (.OH) at physiological pH is chemically feasible. UVA irradiated SCC-13 cells induced a luminol-enhanced chemiluminescence signal that reaches a peak within 1 min. The modulation of this signal by ebselen is consistent with a rate-determining step corresponding to the disproportionation of a luminol-superoxide (O2-) complex. UVA irradiated SCC-13 cells promptly increased malondialdehyde (MDA) production with subsequent decrease of plasma membrane fluidity. Desferrioxamine tested in UVA irradiated SCC-13 cells showed a concentration dependent decrease in MDA production with subsequent restoration of the membrane fluidity to the normal level. Furthermore, it was shown that squamous cell carcinoma possesses higher NO synthase and sGC activity as compared to normal keratinocytes. Such an increase in NO production may be directly related to the poor prognosis of squamous cell carcinoma.