Michiels C, Arnould T, Knott I, Dieu M, Remacle J
Laboratoire de Biochimie Cellulaire, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Am J Physiol. 1993 Apr;264(4 Pt 1):C866-74. doi: 10.1152/ajpcell.1993.264.4.C866.
In ischemic organs, arachidonic acid (AA) metabolites and mostly prostaglandins (PGs) have been found to be released in high amounts. The mechanism for this AA metabolism activation and its physiological implications are not clear. Because endothelial cells are an important source of PGs and because they seem to be very rapidly affected by ischemia, we developed an in vitro model where human endothelial cells were submitted to hypoxia. An important specific activation of phospholipase A2 was observed during hypoxia, which was concomitant with a rise in cytosolic calcium concentration. Endothelial cells synthetize in normal conditions as a mean 1.42, 1.00, 7.69, and 26.92 ng/mg proteins of, respectively, PGE2, PGD2, PGF2 alpha, PGI2. An important increase of about five- to ninefold in the synthesis of the four PGs was observed during hypoxia, which followed the same kinetics as the PLA2 activation. This increase in PG synthesis was sensitive to cyclooxygenase inhibitors. During reoxygenation, PG synthesis decreased back to the basal level of resting cells, suggesting that cells were able to recover their homeostasis after hypoxia. These observations indicate that endothelial cells exposed to oxygen deprivation are a major source of PGs and could contribute to the high amounts of PG released in vivo in ischemic organs.
在缺血器官中，已发现大量释放花生四烯酸（AA）代谢产物，主要是前列腺素（PGs）。这种AA代谢激活的机制及其生理意义尚不清楚。由于内皮细胞是PGs的重要来源，且似乎极易受到缺血影响，我们建立了一个体外模型，将人内皮细胞置于缺氧环境中。缺氧期间观察到磷脂酶A2的重要特异性激活，这与胞质钙浓度升高同时发生。在正常条件下，内皮细胞分别合成平均为1.42、1.00、7.69和26.92 ng/mg蛋白质的PGE2、PGD2、PGF2α、PGI2。缺氧期间观察到这四种PGs的合成增加了约五至九倍，其动力学与PLA2激活相同。PG合成的这种增加对环氧化酶抑制剂敏感。再给氧期间，PG合成恢复到静息细胞的基础水平，表明细胞在缺氧后能够恢复其稳态。这些观察结果表明，暴露于缺氧环境的内皮细胞是PGs的主要来源，可能导致缺血器官在体内释放大量PGs。
