Zhu Ting, Chen Rui, Li Aiping, Liu Jia, Gu Dengan, Liu Qizhan, C Chang Hebron, Zhou Jianwei
Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratories of Human Functional Genomics and of Applied Toxicology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
J Toxicol Environ Health A. 2006 Aug;69(15):1399-411. doi: 10.1080/15287390500360612.
Previous data showed that JWA might be a novel environmental responsive gene regulated by environmental stressors such as heat shock and oxidative stress. However, the molecular mechanism underlying JWA gene function involved in oxidative stress is still unknown. In this study, the potential role of JWA was further investigated in hydrogen peroxide (H2O2) induced DNA damage and cell apoptosis in K562 cells. Series of the oxidative stress models were established to observe if JWA was involved in DNA damage or cell apoptosis induced by H2O2 exposure. These results indicated that the inhibitory effect on K562 cells' viability induced by H2O2 was concentration and time dependent. JWA was more sensitive to H2O2 (0.01 mmol/L) than the heat-shock proteins (hsp70 and hsp27), and its expression pattern was similar to that of hsp70. In addition, JWA, hsp70, hsp27, and p53 were overexpressed and the expression patterns of JWA, hsp70, and p53 were similar during cell apoptosis. H2O2 led to the cleavage and activation of procaspase-3. In conclusion, these results suggested that JWA might be an effective environmental responsive gene that functions as a parallel with hsp70 in oxidative stress-responsive pathways in K562 cells. Like hsp70, JWA might enhance intracellular defenses and function against H2O2-induced oxidative stress in leukemia cells. At the same time, JWA was involved in the p53-associated signal pathways of oxidative stress-induced apoptosis, which is also caspase-3 dependent.
先前的数据表明，JWA可能是一种受热休克和氧化应激等环境应激因素调控的新型环境响应基因。然而，JWA基因在氧化应激中发挥作用的分子机制仍不清楚。在本研究中，进一步探讨了JWA在过氧化氢（H2O2）诱导的K562细胞DNA损伤和细胞凋亡中的潜在作用。建立了一系列氧化应激模型，以观察JWA是否参与H2O2暴露诱导的DNA损伤或细胞凋亡。这些结果表明，H2O2对K562细胞活力的抑制作用呈浓度和时间依赖性。JWA对H2O2（0.01 mmol/L）比热休克蛋白（hsp70和hsp27）更敏感，其表达模式与hsp70相似。此外，在细胞凋亡过程中，JWA、hsp70、hsp27和p53均过表达，且JWA、hsp70和p53的表达模式相似。H2O2导致procaspase-3的切割和激活。总之，这些结果表明，JWA可能是一种有效的环境响应基因，在K562细胞的氧化应激反应途径中与hsp70发挥平行作用。与hsp70一样，JWA可能增强细胞内防御功能，抵抗白血病细胞中H2O2诱导的氧化应激。同时，JWA参与了氧化应激诱导凋亡的p53相关信号通路，这也是caspase-3依赖性的。
