Nitric oxide protects human extravillous trophoblast cells from apoptosis by a cyclic GMP-dependent mechanism and independently of caspase 3 nitrosylation
Nitric oxide protects human extravillous trophoblast cells from apoptosis by a cyclic GMP-dependent mechanism and independently of caspase 3 nitrosylation
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DOI：
10.1016/s0014-4827(03)00156-3
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发表时间：
2003-07-15
影响因子：
3.7
通讯作者：
Whitley, GSJ
中科院分区：
文献类型：
--
作者：
Dash, PR;Cartwright, JE;Whitley, GSJ
细胞凋亡被认为在胎盘发育中起着重要的调节作用，并且不适当的滋养细胞凋亡与妊娠并发症如先兆子痫有关。在这里，我们表明人绒毛外滋养层细胞衍生细胞系（SGHPL-4）的细胞凋亡可以受到一氧化氮（NO）的调节。通过添加NO供体外源性产生的一氧化氮能够延迟或抑制由肿瘤坏死因子a和放线菌素D的组合诱导的细胞凋亡，并抑制caspase 3的活性。用肝细胞生长因子（HGF）处理刺激诱导型NO合酶亚型的表达，也能够保护SGHPL-4细胞免于caspase 3激活和凋亡。用NO合成酶抑制剂抑制基础NO产生显示出使细胞对凋亡刺激物敏感并降低内源性半胱天冬酶3亚硝基化的水平。NO在这些绒毛外滋养层细胞中的抗凋亡作用似乎是通过产生环GMP介导的，因为可溶性鸟苷酸环化酶抑制剂抑制了HGF和NO供体的保护作用。(C)2003 Elsevier Science（美国）。All rights reserved.
Apoptosis is thought to play an important regulatory role in placental development and inappropriate trophoblast apoptosis has been implicated in complications of pregnancy such as pre-eclampsia. Here we show that apoptosis of a human extravillous trophoblast-derived cell line (SGHPL-4) can be regulated by nitric oxide (NO). Nitric oxide produced exogenously by the addition of NO donors was able to delay or inhibit apoptosis induced by a combination of tumour necrosis factor a and actinomycin D and to suppress the activity of caspase 3. Treatment with hepatocyte growth factor (HGF) stimulated expression of the inducible isoform of NO synthase and was also able to protect SGHPL-4 cells from caspase 3 activation and apoptosis. The inhibition of basal NO production with NO synthase inhibitors was shown to sensitise cells to apoptotic stimuli and to reduce the level of endogenous caspase 3 nitrosylation. The anti-apoptotic effects of NO in these extravillous trophoblast cells appear to be mediated through the production of cyclic GMP as inhibitors of soluble guanylate cyclase inhibited the protective effect of both HGF and NO donors. (C) 2003 Elsevier Science (USA). All rights reserved.