Sánchez de Medina Fermín, Martínez-Augustin Olga, González Raquel, Ballester Isabel, Nieto Ana, Gálvez Julio, Zarzuelo Antonio
Department of Pharmacology, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Biochem Pharmacol. 2004 Dec 15;68(12):2317-26. doi: 10.1016/j.bcp.2004.07.045.
This study demonstrates the upregulation of alkaline phosphatase and the mechanisms involved in experimental colitis. All models of ileal and colonic inflammation examined, which were characterized by significant oxidative stress and neutrophil infiltration, resulted in an increase in alkaline phosphatase activity which was attributable to both epithelial cells and cells of the lamina propria, mainly leukocytes. The increase in alkaline phosphatase sensitivity to the inhibitors levamisole and homoarginine, together with changes in the apparent molecular size and in the sialization of the enzyme, indicated a change in the isoform expressed. An increase in tissue non-specific alkaline phosphatase expression was observed by Western blotting. Treatment with the bone/kidney alkaline phosphatase inhibitor levamisole or a monoclonal antibody resulted in significant protection from colonic inflammation. Taken together, these results indicate that the kidney isoform is a marker of intestinal inflammation and that it might even constitute a target for pharmacological intervention.
本研究证实了碱性磷酸酶的上调及其在实验性结肠炎中的相关机制。所检测的所有回肠和结肠炎症模型均以显著的氧化应激和中性粒细胞浸润为特征，这些模型均导致碱性磷酸酶活性增加，这归因于上皮细胞和固有层细胞，主要是白细胞。碱性磷酸酶对抑制剂左旋咪唑和高精氨酸的敏感性增加，以及酶的表观分子大小和唾液酸化的变化，表明所表达的同工型发生了改变。通过蛋白质印迹法观察到组织非特异性碱性磷酸酶表达增加。用骨/肾碱性磷酸酶抑制剂左旋咪唑或单克隆抗体进行治疗可显著预防结肠炎症。综上所述，这些结果表明肾脏同工型是肠道炎症的标志物，甚至可能构成药物干预的靶点。
