González Antonio, Schmid Andreas, Salido Ginés M, Camello Pedro J, Pariente José A
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, P.O. Box 643 10071, Cáceres, Spain.
Cell Signal. 2002 Feb;14(2):153-9. doi: 10.1016/s0898-6568(01)00247-9.
In fura-2 loaded isolated mouse pancreatic acinar cells, xanthine oxidase (XOD)-catalyzed reactive oxygen species (ROS) generation caused an increase in the cytosolic Ca(2+) concentration (Ca(2+)) by release of Ca(2+) from intracellular stores. The ROS-induced Ca(2+) signals showed large variability in shape and time-course and resembled in part Ca(2+) signals in response to physiological secretagogues. ROS-induced Ca(2+) mobilization started at the luminal cell pole and spread towards the basolateral side in a wave manner. ROS-evoked Ca(2+) responses were not inhibited by the phospholipase C (PLC) inhibitor U73122 (10 microM). Neither 2-aminoethoxy-diphenylborate (2-APB) (70 microM) nor ryanodine (50 microM) suppressed ROS-evoked Ca(2+) release. ROS still released Ca(2+) when the endoplasmic reticulum Ca(2+)-ATPase was blocked with thapsigargin (1 microM), or when rotenone (10 microM) was added to release Ca(2+) from mitochondria. Our results suggest that pancreatic acinar cells ROS do not unspecifically affect Ca(2+) homeostasis. ROS primarily affect Ca(2+) stores located in the luminal cell pole, which is also the trigger zone for agonist-induced Ca(2+) signals. Release of Ca(2+) induces Ca(2+) waves carried by Ca(2+)-induced Ca(2+) release and produces thereby global Ca(2+) signals. Under oxidative stress conditions, the increase in Ca(2+) could be one mechanism contributing to an overstimulation of the cell which could result in cell dysfunction and cell damage.
在装载了fura-2的分离小鼠胰腺腺泡细胞中，黄嘌呤氧化酶（XOD）催化的活性氧（ROS）生成通过从细胞内储存库释放Ca(2+)导致胞质Ca(2+)浓度（[Ca(2+)]i）升高。ROS诱导的Ca(2+)信号在形状和时间进程上表现出很大的变异性，部分类似于对生理促分泌剂的Ca(2+)信号。ROS诱导的Ca(2+)动员始于细胞腔极，并以波的方式向基底外侧扩散。ROS诱发的Ca(2+)反应不受磷脂酶C（PLC）抑制剂U73122（10 microM）的抑制。2-氨基乙氧基二苯硼酸盐（2-APB）（70 microM）和ryanodine（50 microM）均未抑制ROS诱发的Ca(2+)释放。当内质网Ca(2+)-ATP酶被毒胡萝卜素（1 microM）阻断时，或者当鱼藤酮（10 microM）被添加以从线粒体释放Ca(2+)时，ROS仍能释放Ca(2+)。我们的结果表明，胰腺腺泡细胞中的ROS不会非特异性地影响Ca(2+)稳态。ROS主要影响位于细胞腔极的Ca(2+)储存库，而细胞腔极也是激动剂诱导的Ca(2+)信号的触发区。Ca(2+)的释放诱导由Ca(2+)诱导的Ca(2+)释放所携带的Ca(2+)波，从而产生全局Ca(2+)信号。在氧化应激条件下，[Ca(2+)]i的升高可能是导致细胞过度刺激的一种机制，这可能导致细胞功能障碍和细胞损伤。
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