Monari M, Foschi J, Calabrese C, Liguori G, Di Febo G, Rizzello F, Gionchetti P, Trinchero A, Serrazanetti G P
Dipartimento di Biochimica G. Moruzzi, Facoltà Medicina Veterinaria, Università di Bologna, I-40064 Ozzano Emilia, Bologna, Italy.
Int J Mol Med. 2009 Nov;24(5):693-700. doi: 10.3892/ijmm_00000281.
The present study is the first to evaluate the expression and activity of MnSOD, Cu/ZnSOD and catalase in human gastric samples, since ROS play a significant role in the pathogenesis of different forms of malignancy inducing mutations and various diseases such as gastric cancer. Biopsies and surgical samples from 53 patients (male/female 22/31, mean age 56.5+/-15.8 years) consisted of 15 healthy, 12 autoimmune atrophic gastritis, 10 Helicobacter pylori (HP) infection, 8 HP-negative chronic gastritis (CG) and 8 adenocarcinoma cases. Enzyme activity and expression were evaluated by spectrophotometry and immunoblotting after specific extraction in phosphate buffer. We found that MnSOD activity was increased in adenocarcinoma, CG and HP tissues (p<0.05-0.001), while Cu/ZnSOD was significantly lower in adenocarcinoma and HP tissues (p<0.001) when compared to the healthy control. MnSOD and Cu/ZnSOD were expressed to a significantly higher degree in adenocarcinoma and HP tissues (p<0.05 and <0.001 respectively) and to a significantly lower degree in CG tissues with respect to the healthy patients (p<0.05 and <0.001). A significant decrease in CAT activity in adenocarcinoma and HP tissues was observed (p<0.01 and <0.05). Gastric human neoplasms showed significant changes in antioxidant enzymes, that represent the first line in antioxidant protection against radical attack. The difficulties in correlating the antioxidant enzyme with the neoplasms was related to the complexity of the biochemical pathways that regulate the cellular redox balance. Our results are important in enhancing the understanding of the role that these enzymes play in the promotion/suppression of the carcinogenesis cascade in human gastric mucosa.
本研究首次评估了人胃样本中锰超氧化物歧化酶(MnSOD)、铜/锌超氧化物歧化酶(Cu/ZnSOD)和过氧化氢酶的表达及活性,因为活性氧(ROS)在不同形式恶性肿瘤的发病机制中发挥着重要作用,可诱发突变以及引发各种疾病,如胃癌。53例患者(男/女为22/31,平均年龄56.5±15.8岁)的活检及手术样本包括15例健康样本、12例自身免疫性萎缩性胃炎样本、10例幽门螺杆菌(HP)感染样本、8例HP阴性慢性胃炎(CG)样本以及8例腺癌样本。在磷酸盐缓冲液中进行特定提取后,通过分光光度法和免疫印迹法评估酶活性及表达情况。我们发现,与健康对照相比,腺癌、CG和HP组织中的MnSOD活性升高(p<0.05 - 0.001),而腺癌和HP组织中的Cu/ZnSOD显著降低(p<0.001)。MnSOD和Cu/ZnSOD在腺癌和HP组织中的表达显著更高(分别为p<0.05和<0.001),而与健康患者相比,CG组织中的表达显著更低(p<0.05和<0.001)。观察到腺癌和HP组织中的CAT活性显著降低(p<0.01和<0.05)。胃人类肿瘤显示出抗氧化酶的显著变化,这些酶是抗氧化保护免受自由基攻击的第一道防线。将抗氧化酶与肿瘤相关联存在困难,这与调节细胞氧化还原平衡的生化途径的复杂性有关。我们的结果对于增强理解这些酶在人类胃黏膜致癌级联反应的促进/抑制中所起的作用具有重要意义。