Park Jung Je, Chang Hyo Won, Jeong Eun-Jeong, Roh Jong-Lyel, Choi Seung-Ho, Jeon Sea-Yuong, Ko Gyung Hyuck, Kim Sang Yoon
Department of Otolaryngology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, South Korea.
Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1196-202. doi: 10.1016/j.ijrobp.2008.10.070.
Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR).
To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay.
Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis.
The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma.
人过氧化物还原酶(Prxs)是一类硫醇特异性抗氧化酶,其中Prx-I和-II在保护细胞免受辐射诱导的细胞死亡中起重要作用。目前尚不清楚Prx-IV是否也能保护细胞免受电离辐射(IR)。
为了评估Prx-IV在IR中的保护作用,我们将全长Prx-IV cDNA转染到内源性Prx-IV表达较弱的AMC-HN3细胞中,并使用内源性Prx-IV表达水平较高的AMC-HN7细胞,通过小干扰RNA(siRNA)方法敲低Prx-IV的表达。使用克隆形成试验、流式细胞术分析、细胞活力和TUNEL试验评估这些细胞的放射敏感性。
分离出三个表达Prx-IV的克隆。Prx-IV调节细胞内活性氧(ROS)水平,使细胞对IR诱导的凋亡更具抗性。此外,用siRNA敲低Prx-IV使细胞对IR诱导的凋亡更敏感。
这些研究结果表明,Prx-IV可能在保护头颈部鳞状细胞癌细胞免受IR诱导的凋亡中起重要作用。