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p53基因是迄今发现与人类肿瘤相关性最高的基因, 在短短的十多年里, 人们对p53基因的认识经历了癌蛋白抗原、癌基因、抑癌基因3个认识的转变。50%以上的恶性肿瘤会出现该基因的突变。最近的研究发现, p53基因在能量代谢方面具有重要的调节作用, 它可被单磷酸腺苷活化蛋白激酶(adenosine monophosphate activated potein kinase, AMPK)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)通路调节的代谢应激所激活, 在病理和正常的生理状况下通过平衡糖酵解和氧化磷酸化调节能量代谢、氧化应激和氨基酸代谢, 例如, p53基因可通过调节2, 6-双磷酸果糖激酶、p53诱导基因TP53诱导的糖酵解和凋亡调节因子(TP53-induced glycolysis and apoptosis regulator, TIGAR)和电子传递链上复合体IV的亚单位细胞色素C氧化酶转录来调节氧化磷酸化[1], 也可通过调节葡萄糖载体谷氨酰胺酶2和脂肪酸合酶的表达来间接地影响能量代谢。另一方面, p53基因的功能状态及其相应的能量代谢改变在电离辐射诱发肿瘤的过程中具有举足轻重的作用, p53基因状态的改变使得DNA受损细胞不能得到及时修复或清除, 成为诱发肿瘤的机制之一。本文对p53基因在能量代谢中的作用及其分子机制和与电离辐射生物效应的关系进行了简要综述。
p53调控的能量代谢对辐射效应的影响
Influence of p53-regulated energy metabolism in radiation effects
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摘要: p53基因一直是肿瘤病因学、放射生物学的研究热点, 但受其调控的能量代谢在辐射生物效应中的作用还存在许多未知因素。了解p53基因调控的能量代谢对探讨肿瘤放射治疗疗效、辐射损伤、辐射致癌的早期筛选生物指标和分子流行病学调查均有着极其重要的意义。该文概述了此方面的研究进展。Abstract: p53 is a hot spot in the studies of tumor etiology and radiobiology, but the function of p53-reguated energy metabolism in radiation biological effects still remains many uncertainties. The in-depth study of p53-regulated energy metabolism is of great significance to investigate the tumor radiotherapy efficacy, radiation damage, carcinogenesis and even molecular epidemiology. The current research progress at this point was stated in this article.
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Key words:
- Genes, p53 /
- Energy metabolism /
- Radiation effects /
- Neoplasms /
- Radiotherapy
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