Nishihata T, Caldwell L J, Sakai K
Pharmaceutical Chemistry Department, University of Kansas, Lawrence 66046.
Biochim Biophys Acta. 1988 Jun 8;970(1):7-18. doi: 10.1016/0167-4889(88)90216-9.
Studies on the mechanism of chemically induced intestinal epithelial injury were carried out using isolated, rat small intestinal epithelial cells. Compounds such as 2,4-dinitrophenol (DNP) and diethyl maleate (DEM), caused NADH loss, an increase in cytosolic Ca2+ concentration and protein thiol loss. Further, these compounds accelerated cell aggregation and decreased cell viability. Calmodulin antagonists inhibited protein thiol loss induced by either of the compound, inhibited cell aggregation and prolonged cell viability, but did not influence NADH loss. It has been reported that the calmodulin-binding protein may regulate cytoskeletal activity. Therefore, the inhibition of protein thiol loss by calmodulin antagonist may be due to a dissociation of calmodulin-binding proteins from cytoskeletal elements. Salicylate also inhibited protein thiol loss induced by DNP and DEM, and inhibited cell aggregation. However, salicylate may have a direct effect in reducing the cytosolic free Ca2+ concentration by complexation and subsequent facilitated release of Ca2+ from cells. Further, in the present study, the induction of cell aggregation may be caused by the appearance of specific sites on the cell membrane surface to which arsenazo III could adsorb, since adsorption of arsenazo III to the isolated epithelial cells seemed to correlate with increased cell aggregation.
利用分离的大鼠小肠上皮细胞对化学诱导的肠道上皮损伤机制进行了研究。2,4 -二硝基苯酚（DNP）和马来酸二乙酯（DEM）等化合物会导致NADH损失、胞质Ca2+浓度升高以及蛋白质巯基损失。此外，这些化合物会加速细胞聚集并降低细胞活力。钙调蛋白拮抗剂可抑制这两种化合物诱导的蛋白质巯基损失，抑制细胞聚集并延长细胞活力，但不影响NADH损失。据报道，钙调蛋白结合蛋白可能调节细胞骨架活性。因此，钙调蛋白拮抗剂对蛋白质巯基损失的抑制作用可能是由于钙调蛋白结合蛋白与细胞骨架成分解离所致。水杨酸盐也可抑制DNP和DEM诱导的蛋白质巯基损失，并抑制细胞聚集。然而，水杨酸盐可能通过络合作用直接降低胞质游离Ca2+浓度，并随后促进Ca2+从细胞中释放。此外，在本研究中，细胞聚集的诱导可能是由于细胞膜表面出现了偶氮胂III可以吸附的特定位点，因为偶氮胂III对分离的上皮细胞的吸附似乎与细胞聚集增加相关。
