Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour.
Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour.
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DOI：
10.1038/sj.bjc.6600830
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发表时间：
2003-03-24
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
血红素加氧酶-1（HO-1）的诱导可能对细胞抗氧化应激提供重要的保护作用。在这里，我们研究了HO-1在实体瘤中的细胞保护机制，重点是HO-1的抗凋亡活性。HO抑制剂锌原卟啉IX（ZnPP IX）或锡原卟啉IX的大鼠肝癌AH 136 B细胞的治疗导致广泛的肿瘤细胞在体内和体外的凋亡变化。ZnPP IX处理的肝癌细胞的Caspase-3活性显著增加。此外，ZnPP IX诱导的细胞凋亡被完全抑制，同时与特定的caspase-3抑制剂孵育，并部分废除胆红素，HO的反应产物。体内ZnPP IX治疗不影响一氧化氮（NO）的产生和肿瘤血流。Western blot分析显示，HO-1在AH 136 B细胞中的表达在体外被NO供体如S-亚硝基-N-乙酰青霉胺和丙胺NONOate强烈上调;相反，在体内被NOS的药理学阻断显著降低。我们得出结论，HO-1可能在肿瘤的抗凋亡防御中发挥作用，因此它可能对肿瘤细胞对抗NO诱导的氧化应激具有重要的保护和有益作用，NO在体内实体瘤生长过程中过量产生。
Induction of haem oxygenase-1 (HO-1) may provide an important protective effect for cells against oxidative stress. Here, we investigated the mechanism of cytoprotection of HO-1 in solid tumour with a focus on the antiapoptotic activity of HO-1. Treatment of rat hepatoma AH136B cells with the HO inhibitor zinc protoporphyrin IX (ZnPP IX) or tin protoporphyrin IX resulted in extensive apoptotic changes of tumour cells both in vivo and in vitro. Caspase-3 activity of the ZnPP IX-treated hepatoma cells increased significantly. Moreover, ZnPP IX-induced apoptosis was completely inhibited by simultaneous incubation with a specific caspase-3 inhibitor and was partially abrogated by bilirubin, a reaction product of HO. In vivo ZnPP IX treatment did not affect nitric oxide (NO) production and tumour blood flow. Western blot analyses showed that HO-1 expression in AH136B cells was strongly upregulated by NO donors, for example, S-nitroso-N-acetyl penicillamine and propylamine NONOate in vitro; conversely, it was remarkably reduced in vivo by pharmacological blockade of NOS. We conclude that HO-1 may function in antiapoptotic defense of the tumour, and thus it may have important protective and beneficial effects for tumour cells against oxidative stress induced by NO, which is produced in excess during solid tumour growth in vivo.
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影响因子：
4.7
作者：
Sahoo, SK;Sawa, T;Maeda, H
通讯作者：
Maeda, H
影响因子：
82.9
作者：
Hancock, WW;Buelow, R;Turka, LA
通讯作者：
Turka, LA
影响因子：
64.5
作者：
MANNICK, JB;ASANO, K;STAMLER, JS
通讯作者：
STAMLER, JS
DOI：
10.1073/pnas.92.10.4392
发表时间：
1995-05-09
影响因子：
11.1
作者：
JENKINS, DC;CHARLES, IG;MONCADA, S
通讯作者：
MONCADA, S
影响因子：
4.8
作者：
Bouton, C;Demple, B
通讯作者：
Demple, B