王魁 明慧 左静 田海隆 黄灿华

王魁, 明慧, 左静, 等. 氧化还原信号调控与肿瘤代谢[J]. 四川大学学报(医学版), 2021, 52(1): 57-63. doi: 10.12182/20210160204
引用本文: 王魁, 明慧, 左静, 等. 氧化还原信号调控与肿瘤代谢[J]. 四川大学学报(医学版), 2021, 52(1): 57-63. doi: 10.12182/20210160204
WANG Kui, MING Hui, ZUO Jing, et al. A Review of the Redox Regulation of Tumor Metabolism[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 57-63. doi: 10.12182/20210160204
Citation: WANG Kui, MING Hui, ZUO Jing, et al. A Review of the Redox Regulation of Tumor Metabolism[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 57-63. doi: 10.12182/20210160204

栏目: 综 述


doi: 10.12182/20210160204
基金项目: 国家自然科学基金(No. 81821002、No. 81790251、No. 81872277、No. 82073081),国家重点研发计划(No. 2020YFA0509400、No. 2020YFC2002705),广东省基础与应用基础研究重大项目(No. 2019B030302012)和四川省科技计划项目(No. 2020YJ0107)资助


A Review of the Redox Regulation of Tumor Metabolism

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  • 摘要: 代谢异常是肿瘤细胞的十大特征之一,肿瘤细胞能够通过代谢重编程满足其快速增殖的物质和能量需求。肿瘤代谢重编程伴随活性氧(reactive oxygen species,ROS)的产生以及抗氧化体系的激活。ROS含量过高会导致氧化损伤甚至细胞死亡,而适量水平的ROS可作为第二信使参与调控多种信号通路。近年来,随着对氧化应激研究的不断深入,发现ROS可直接介导蛋白质发生氧化还原修饰(redox modifications),从而造成蛋白质构象或功能的改变。然而,目前仅报道了3-磷酸甘油醛脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GAPDH)、M2型丙酮酸激酶(PKM2)等个别代谢酶的氧化还原修饰,其他代谢酶是否受到氧化还原修饰调控并发挥重要功能尚不清楚,靶向代谢酶氧化还原修饰的时空特异性和代偿适应性也是目前的重点和难点。本文将从肿瘤代谢的角度出发,综述近年来报道的有关代谢酶的氧化还原修饰模式、调控机制及其在肿瘤发生发展中的作用,探讨和展望靶向代谢酶氧化还原修饰的肿瘤治疗策略。
  • 图  1  蛋白质的氧化还原修饰翻译模式

    Figure  1.  The redox modification patterns of protein cysteines

    ROS can induce the redox modifications of thiols on the cysteines of proteins. The redox modification patterns include sulfenylation (RSOH), disulfide (RS-SR or RS-SR') formation, S-glutathionylation (RS-SG), sulfinylation (RSO2H) and sulfonylation (RSO3H).

    图  2  代谢酶的氧化还原修饰模式

    Figure  2.  Oxidative modifications of metabolic enzymes

    In response to ROS-mediated oxidative stress, many metabolic enzymes can undergo redox modifications, including glycolytic enzymes (HK1, TPI, GAPDH, ENO, PKM2, and PDHK2, etc.), TCA cycle enzymes (Aconitase, PDHK2, etc.), lipid metabolism enzymes (ACAT2, TPβ, etc.), energy metabolism enzymes (AMPK, CK, etc.), and amino acid metabolism enzymes (CBS, etc.), leading to the alteration of metabolic patterns.

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  • 收稿日期:  2020-11-09
  • 修回日期:  2020-12-29
  • 刊出日期:  2021-01-20