Rosado Juan A, González Antonio, Salido Ginés M, Pariente Jose A
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Cáceres 10071, Spain.
Cell Signal. 2002 Jun;14(6):547-56. doi: 10.1016/s0898-6568(01)00273-x.
The present study investigates the effect of reactive oxygen species (ROS) on actin filament reorganisation and its relevance to exocytosis in pancreatic acinar cells. Treatment of pancreatic acini with cholecystokinin (CCK-8) induced spatial and temporal changes in actin filament reorganisation with an initial depolymerisation of the apical actin barrier followed by an increase in the actin filament content in the subapical area leading to amylase release. Hydrogen peroxide (H(2)O(2)) increased actin filament content and potentiated the polymerizing effects of CCK-8 in these cells but abolished the disruption of the apical actin layer and amylase release induced by CCK-8. Similar to CCK-8, ROS generated by the oxidation of hypoxanthine (HX) with xanthine oxidase (XOD) induced an initial decrease in actin filaments located under the apical membrane followed by a smaller increase in the content of actin filaments in the subapical area. XOD-generated ROS are able to increase amylase release in pancreatic acini although combination with CCK-8 leads to abnormal exocytosis. We provide evidence that indicates that CCK-8- and ROS-induced actin reorganisation is entirely dependent on Ca(2+) mobilisation and independent of PKC activation. The regulation of the actin cytoskeleton by ROS might be involved in radical-induced cell injury in pancreatic acinar cells.
本研究调查了活性氧（ROS）对胰腺腺泡细胞中肌动蛋白丝重组的影响及其与胞吐作用的相关性。用胆囊收缩素（CCK-8）处理胰腺腺泡，可诱导肌动蛋白丝重组发生时空变化，首先是顶端肌动蛋白屏障解聚，随后是顶端下区域肌动蛋白丝含量增加，导致淀粉酶释放。过氧化氢（H₂O₂）增加了肌动蛋白丝含量，并增强了CCK-8对这些细胞的聚合作用，但消除了CCK-8诱导的顶端肌动蛋白层破坏和淀粉酶释放。与CCK-8相似，次黄嘌呤（HX）与黄嘌呤氧化酶（XOD）氧化产生的ROS导致顶端膜下肌动蛋白丝最初减少，随后顶端下区域肌动蛋白丝含量略有增加。XOD产生的ROS能够增加胰腺腺泡中的淀粉酶释放，尽管与CCK-8联合使用会导致异常胞吐。我们提供的证据表明，CCK-8和ROS诱导的肌动蛋白重组完全依赖于Ca²⁺动员，且与蛋白激酶C（PKC）激活无关。ROS对肌动蛋白细胞骨架的调节可能参与了胰腺腺泡细胞中自由基诱导的细胞损伤。
