Reactive Oxygen Species (ROS) have a well-established role in the pathogenesis of many forms of malignancy and superoxide dismutase (SOD) is the only enzyme dismuting the superoxide anion.Parallel the mitochondrial and peroxisomal catalase (CAT) decomposes hydrogen peroxide to water and molecular oxygen. The Cytochrome P4501A1 is a member of a mùltigene family P450 superfamily (CYPs) of enzyme involved in the oxidative activation/detoxification of drugs and carcinogens.CYPs can produce ROS and reactive metabolite which can form DNA adduct, mutations and several diseases included gastric cancer. The complex network that is known to occur between SOD, CAT and P450 can be considered the starting point for this research. Since many human tumors have shown significai changes in SODs, CAT and P450 that might be correlated with clinical-pathological parameters for thè prognosis of human carcinoma, we have investigate SODs, CAT and CYP1A1/1A2 in adenocarcinoma, Helicobacter pilory (HP), autoimmune-atrophic-gastritis (AAG) and healthy tissues. A total of 32 gastric specimens (6 adenocarcinomas, 11 healthy samples, 8 HP and 7 AAG affected gastric mucosa samples) collected during endoscopy or resected during surgery were extracted and used to perform SOD, CAT activity and SODs and CYP1A1/1A2 expression (western blotting: WB). MnSOD activity was similar in healthy tissues and in AAG tissues: each isoform represents nearly thè 50% of total SOD. On thè contrary thè MnSOD activity was over 9-fold and 2-fold higher with respect to CuZnSOD in tumors and HP samples, respectively. In adenocarcinomas the MnSOD represent almost the 89% of the total SOD activity. After WB, MnSOD seems to be more expressed in adenocarcinoma respect to healthy and AAG tissues (p < 0.01 ) and in HP respect to AAG tissues (p < 0.05). The levels of CuZnSOD were similar in tumor, healthy and HP tissues while was significantly low expressed in AAG tissues (p < 0.01 ). With regard to thè ECSOD expression our preliminary data showed a similar trend in all the considered conditions. CAT activity was significantly higher in healthy tissues respect to other conditions. The CYP1A1/1A2 showed a similar expression in HP, AAG and healthy tissues and a significant suppression (p < 0.05) in adenocarcinoma cases respect to the former conditions. The ratio of MnSOD/CuZnSOD activities and of the two isoforms/total SOD and the P450 suppression seems to be more explicative in the identification of cancer respect to the other condition. The MnSOD induction was imputable to oxidative stress and inflammatory cytokines, while the CYP1A1/1A2 suppression was probably due to cytokines, drugs, ROS produced during the P450 catalytic cycle and hypoxic conditions typical of tumour mass. The SOD and CAT activities and the SODs and CYP expression may be of relevance in the understanding of the roles of specific protein in gastric cancer with a prognostic significance. In conclusion WB and activity assays might provide specific and sensible methods of analysis that allow to differentiate healthy from tumor, AAG and HP tissues.
M. Monari, J. Foschi, C. Calabrese, A. Fabbri, D. Zahalane, G. Di Febo, et al. (2006). The role of SOD, CAT and CYP1A1/1A2 in human gastric neoplasm.. s.l : s.n.
The role of SOD, CAT and CYP1A1/1A2 in human gastric neoplasm.
MONARI, MARTA;DI FEBO, GIULIO;TUGNOLI, VITALIANO;TRINCHERO, ANDREA;SERRAZANETTI, GIAN PAOLO
2006
Abstract
Reactive Oxygen Species (ROS) have a well-established role in the pathogenesis of many forms of malignancy and superoxide dismutase (SOD) is the only enzyme dismuting the superoxide anion.Parallel the mitochondrial and peroxisomal catalase (CAT) decomposes hydrogen peroxide to water and molecular oxygen. The Cytochrome P4501A1 is a member of a mùltigene family P450 superfamily (CYPs) of enzyme involved in the oxidative activation/detoxification of drugs and carcinogens.CYPs can produce ROS and reactive metabolite which can form DNA adduct, mutations and several diseases included gastric cancer. The complex network that is known to occur between SOD, CAT and P450 can be considered the starting point for this research. Since many human tumors have shown significai changes in SODs, CAT and P450 that might be correlated with clinical-pathological parameters for thè prognosis of human carcinoma, we have investigate SODs, CAT and CYP1A1/1A2 in adenocarcinoma, Helicobacter pilory (HP), autoimmune-atrophic-gastritis (AAG) and healthy tissues. A total of 32 gastric specimens (6 adenocarcinomas, 11 healthy samples, 8 HP and 7 AAG affected gastric mucosa samples) collected during endoscopy or resected during surgery were extracted and used to perform SOD, CAT activity and SODs and CYP1A1/1A2 expression (western blotting: WB). MnSOD activity was similar in healthy tissues and in AAG tissues: each isoform represents nearly thè 50% of total SOD. On thè contrary thè MnSOD activity was over 9-fold and 2-fold higher with respect to CuZnSOD in tumors and HP samples, respectively. In adenocarcinomas the MnSOD represent almost the 89% of the total SOD activity. After WB, MnSOD seems to be more expressed in adenocarcinoma respect to healthy and AAG tissues (p < 0.01 ) and in HP respect to AAG tissues (p < 0.05). The levels of CuZnSOD were similar in tumor, healthy and HP tissues while was significantly low expressed in AAG tissues (p < 0.01 ). With regard to thè ECSOD expression our preliminary data showed a similar trend in all the considered conditions. CAT activity was significantly higher in healthy tissues respect to other conditions. The CYP1A1/1A2 showed a similar expression in HP, AAG and healthy tissues and a significant suppression (p < 0.05) in adenocarcinoma cases respect to the former conditions. The ratio of MnSOD/CuZnSOD activities and of the two isoforms/total SOD and the P450 suppression seems to be more explicative in the identification of cancer respect to the other condition. The MnSOD induction was imputable to oxidative stress and inflammatory cytokines, while the CYP1A1/1A2 suppression was probably due to cytokines, drugs, ROS produced during the P450 catalytic cycle and hypoxic conditions typical of tumour mass. The SOD and CAT activities and the SODs and CYP expression may be of relevance in the understanding of the roles of specific protein in gastric cancer with a prognostic significance. In conclusion WB and activity assays might provide specific and sensible methods of analysis that allow to differentiate healthy from tumor, AAG and HP tissues.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
