Differential roles of nitric oxide synthases in regulation of ultraviolet B light-induced apoptosis.
Differential roles of nitric oxide synthases in regulation of ultraviolet B light-induced apoptosis.
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DOI：
10.1016/j.niox.2010.06.003
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Liu W;Wu S
紫外线B光（UVB）激活一氧化氮合酶（NOS）和一氧化氮（NO•）的生成，在细胞凋亡中起调节作用。然而，NO•在uvb诱导的细胞凋亡中的作用仍存在争议。在这项研究中，我们分析了组成NOSs （cNOSs）的表达和激活及其在紫外线诱导的HaCaT角质形成细胞凋亡中的作用。我们的数据显示，在uvb后的早期（0-6 h），神经元NOS （nNOS）的表达增加，而内皮NOS （eNOS）的表达解耦。在uvb后12 h， NO•的表达均达到峰值，30 min后，NO•的表达短暂升高，6 ~ 18 h后，NO•的表达稳步上升。在uvb后6 h检测到iNOS的表达，随后稳定升高。L-NAME对cNOSs的抑制降低了NO•在辐照早期和后期的诱导作用。随着eNOS解耦，在uvb后的早期阶段检测到过氧亚硝酸盐（ONOO−）水平的增加，但在后期阶段没有。在uvb照射后，抑制cNOSs使ONOO−在早期产生减少，但在后期导致ONOO−增加。结果表明，在uvb照射后，cNOSs可调节NO•/ONOO−失衡。我们的数据表明，在uvb后的早期阶段，cNOSs的激活导致NO•/ONOO−失衡，并通过caspase 3非依赖性途径促进细胞凋亡。uvb辐照后期NO•的升高主要是由诱导型NOS （iNOS）产生的。然而，cNOSs也有助于NO•的产生并维持较高的NO•/ONOO−比率，从而降低caspase 3活性并保护细胞免受uvb诱导的凋亡。
Ultraviolet B light (UVB) activates nitric oxide synthase(s) (NOS) and nitric oxide (NO•) production, which plays a role in regulation of apoptosis. However the role of NO• in UVB-induced apoptosis remains controversial. In this study, we analyzed expression and activation of constitutive NOSs (cNOSs) and their roles in UV-induced apoptosis of HaCaT keratinocytes. Our data showed that the expression of neuronal NOS (nNOS) was increased while endothelial NOS (eNOS) was uncoupled in the early phase (0–6 h) post-UVB. The expression of both cNOSs peaked at 12 h post-UVB and NO• was transiently elevated with 30 min and then steadily rose from 6–18 h post-UVB. The expression of iNOS was detected at 6 h post-UVB and then sturdily increased. Inhibition of cNOSs with L-NAME reduced the inducibility of NO• in the early and late phases of irradiation. Along with the eNOS uncoupling, an increased level of peroxynitrite (ONOO−) was detected in the early phase, but not in the late phase post-UVB. Inhibition of cNOSs reduced the production of ONOO− in the early time, but led to an increase of ONOO− in the late time after UVB-irradiation. The results indicate that cNOSs regulate NO•/ONOO− imbalance after UVB-irradiation. Our data suggested that the activation of cNOSs in the early phase post-UVB leads to NO•/ONOO− imbalance and promotes apoptosis via a caspase 3-independent pathway. The elevation of NO• in the late phase of UVB-irradiation is mainly produced by inducible NOS (iNOS). However, cNOSs also contribute to the NO• production and to maintain a higher NO•/ONOO− ratio, which reduces caspase 3 activity and protects cells from UVB-induced apoptosis.
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