Sensitive to apoptosis gene protein regulates ionizing radiation-induced apoptosis
Sensitive to apoptosis gene protein regulates ionizing radiation-induced apoptosis
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DOI：
10.1016/j.biochi.2010.09.020
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发表时间：
2011-02-01
期刊：
影响因子：
3.9
通讯作者：
Park, Jeen-Woo
中科院分区：
文献类型：
--
作者：
Kim, Sung Youl;Yang, Eun Sun;Park, Jeen-Woo
暴露于电离辐射（IR）的生物体会增加活性氧（ROS）的产生，而活性氧是诱导细胞凋亡的决定因素。对凋亡敏感的基因（SAG）编码一种氧化还原诱导和凋亡保护的抗氧化蛋白。本报告表明，在培养细胞中，调节SAG表达可调节ir诱导的细胞凋亡。在转染SAG cDNA的U937细胞中，发现SAG对ir诱导的细胞凋亡具有保护作用。与对照组细胞相比，暴露于2 Gy γ辐射的SAG过表达细胞的内源性ROS产生也显著减少。这些结果表明，SAG可能通过维持细胞氧化还原状态，在调节ir诱导的细胞凋亡中发挥重要作用。由于SAG在许多人类癌症中过度表达，靶向SAG表达可能在癌症治疗中具有治疗价值。用SAG小干扰RNA转染胰腺癌细胞株PC3可显著降低SAG的表达，增强其对ir诱导的凋亡的敏感性。RNA干扰联合放疗降低SAG表达可能是一种潜在的放射增敏方法。(C) 2010 Elsevier Masson SAS。版权所有。
Organisms exposed to ionizing radiation (IR) undergo increases in the production of reactive oxygen species (ROS), which are determinant components in the induction of apoptosis. Sensitive to apoptosis gene (SAG) encodes a redox-inducible and apoptosis-protective antioxidant protein. This report demonstrates that the modulation of SAG expression in cultured cells regulates IR-induced apoptosis. A protective role for SAG against IR-induced apoptosis was found in U937 cells transfected with SAG cDNA. A significant decrease in the endogenous production of ROS was also observed in SAG over-expressing cells, compared to control cells, exposed to 2 Gy gamma-irradiation. These results suggest that SAG plays an important role in regulating IR-induced apoptosis, presumably by maintaining the cellular redox status. Because SAG is over-expressed in many human cancers, targeting SAG expression may have therapeutic value in cancer treatment. Transfection of the pancreatic cancer cell line PC3 with SAG small interfering RNA markedly attenuated the expression of SAG, augmenting their susceptibility to IR-induced apoptosis. The knockdown of SAG expression by RNA interference combined with radiotherapy may be a potential method for radiosensitization. (C) 2010 Elsevier Masson SAS. All rights reserved.