Angiotensin II Induces Oxidative Stress in Prostate Cancer
Angiotensin II Induces Oxidative Stress in Prostate Cancer
复制标题
DOI：
10.1158/1541-7786.mcr-07-0289
复制
发表时间：
2008-02
影响因子：
5.2
通讯作者：
H. Uemura;H. Ishiguro;Yukari Ishiguro;K. Hoshino;Satoru Takahashi;Y. Kubota
中科院分区：
文献类型：
--
作者：
H. Uemura;H. Ishiguro;Yukari Ishiguro;K. Hoshino;Satoru Takahashi;Y. Kubota
血管紧张素II已被证明是一种细胞因子，特别是作为一种生长因子。前列腺中存在局部的肾素-血管紧张素系统，血管紧张素II的生理功能与前列腺癌相似，正如我们以前报道的。在本研究中，我们探讨了血管紧张素II在前列腺癌细胞氧化应激中的生物学作用。激活Akt的测定，并通过蛋白质印迹法在LNCaP细胞中检测氧化应激相关蛋白（p47 phox，锰超氧化物歧化酶2，谷胱甘肽过氧化物酶）的表达，所述LNCaP细胞用血管紧张素II和/或血管紧张素II受体1型阻断剂坎地沙坦刺激。为了检测血管紧张素II诱导的DNA损伤，测定了8-羟基-2 ′-脱氧鸟苷，并分析了Western印迹以检测包括p53、Chk 2和cdc 2在内的检查点蛋白。在血管紧张素II刺激的LNCaP细胞中进行诱导型一氧化氮合酶和超氧阴离子自由基（O2−）的免疫细胞化学研究。Akt的磷酸化被血管紧张素II诱导，并被坎地沙坦和磷酸肌醇3-激酶抑制剂LY 294002抑制。氧化应激相关蛋白的上调血管紧张素II和抑制预处理坎地沙坦或过氧化氢酶。血管紧张素II可增加8-羟基-2 ′-脱氧鸟苷的水平，坎地沙坦可降低8-羟基-2 ′-脱氧鸟苷的水平。免疫细胞化学研究表明，血管紧张素II增强了炎症标志物诱导型一氧化氮合酶和O2−自由基的产生。血管紧张素II有可能诱导氧化应激，这可能是通过长期暴露于慢性炎症前列腺的致癌作用的假说提出。(Mol Cancer Res 2008;6（2）：250-8）
Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2′-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O2−) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2′-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O2− radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed. (Mol Cancer Res 2008;6(2):250–8)