Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis
Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis
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DOI：
10.1080/10253890701314863
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发表时间：
2007-11-01
影响因子：
2.3
通讯作者：
Esposito, F.
中科院分区：
文献类型：
--
作者：
Gesualdi, N. Montesano;Chirico, G.;Esposito, F.
TRAP-1是一种线粒体热休克蛋白（HSP），最近在适应马来酸二乙酯（DEM）诱导的轻度氧化应激的Saos-2骨肉瘤细胞中发现。TRAP-1 mRNA表达在DEM适应细胞以及对5-氟尿嘧啶和铂衍生物耐药的肿瘤细胞中增加。由于顺铂治疗后，TRAP-1蛋白水平的强烈降低仅在对照中观察到，而在DEM适应的对应物中未观察到，因此可以假设该蛋白在耐药表型的发展中的可能作用。为了表征TRAP-1对氧化应激和细胞凋亡的保护作用，产生稳定的转染子并表征其对不同应激类型的响应。这些稳定的克隆表达组成性高水平的TRAP-1：（i）对H2 O2诱导的DNA损伤和顺铂引起的细胞凋亡更有抗性;（ii）含有比对照细胞更高的还原型谷胱甘肽（GSH）水平;和（iii）在顺铂处理后不将细胞凋亡诱导因子释放到细胞核中。此外，高TRAP-1水平干扰半胱天冬酶3活化。这些结果证实了TRAP-1的抗凋亡作用，并表明这种线粒体HSP在DEM适应和化学抗性细胞中的表达增加可能是旨在逃避氧化剂和抗癌药物毒性作用的促生存信号通路的一部分。
TRAP-1 is a mitochondrial heat shock protein (HSP), recently identified in Saos-2 osteosarcoma cells adapted to mild oxidative stress induced by diethylmaleate (DEM). TRAP-1 mRNA expression is increased in DEM-adapted cells as well as in tumor cells resistant to 5-fluorouracil and to platin derivatives. Since a strong decrease of TRAP-1 protein levels, upon cisplatin treatment, is observed only in controls but not in the DEM-adapted counterpart, a possible role for this protein in the development of resistant phenotypes could be hypothesized. To characterize the protective role of TRAP-1 against oxidative stress and apoptosis, stable transfectants were generated and characterized for their response to different stress types. These stable clones expressing constitutively high TRAP-1 levels: (i) are more resistant to H2O2-induced DNA damage and to apoptosis by cisplatin; (ii) contain higher reduced glutathione (GSH) levels than control cells; and (iii) do not release the apoptosis-inducing factor into the nucleus upon cisplatin treatment. Furthermore, high TRAP-1 levels interfere with caspase 3 activation. These results confirm the anti-apoptotic role of TRAP-1, and suggest that increased expression of this mitochondrial HSP in DEM-adapted and chemoresistant cells could be part of a pro-survival signaling pathway aimed to evade toxic effects of oxidants and anticancer drugs.