BIPHASIC EFFECT OF OXYGEN RADICALS ON PROSTAGLANDIN PRODUCTION BY RAT MESANGIAL CELLS
BIPHASIC EFFECT OF OXYGEN RADICALS ON PROSTAGLANDIN PRODUCTION BY RAT MESANGIAL CELLS
复制标题
DOI：
10.1152/ajprenal.1987.252.4.f743
复制
发表时间：
1987-04-01
影响因子：
--
通讯作者：
COUSER, WG
中科院分区：
文献类型：
--
作者：
ADLER, S;STAHL, RAK;COUSER, WG
采用黄嘌呤加黄嘌呤氧化酶的活性氧（ROS）产生系统，观察ROS对大鼠肾小球系膜细胞花生四烯酸（AA）代谢的影响。通过51 Cr释放评估的细胞活力不受所用黄嘌呤加黄嘌呤氧化酶浓度的影响。在暴露于增加量的黄嘌呤加黄嘌呤氧化酶后，前列腺素E2（PGE2）的产生显著降低至38.1 ± 0.01。9.7或30.8 ±。当分别用钙离子载体A23187（1 μ g/ml）或AA（10 - 6 M）刺激细胞时，为对照水平的6.9%（P <0.05）。在ROS暴露的10分钟内观察到产生的最大抑制。血栓素B2的产生同样降低到83.1 ± 0.001。7.6（0.05 <P <0.10）或54.9 ±。2.5%（P <0.05）。这种作用被逆转的过氧化氢酶的ROS产生系统，但不是由超氧化物歧化酶或甘露醇，这表明H2O2是负责代谢产物。高水平的H2O2（5x. 10-4 M）抑制PGE 2产生至44.0 ±. 4.1或17.4 ±。A23187或AA刺激的细胞产生率为6.2%（P <0.05）。较低水平的H2O2导致基线PGE2生产的显着刺激。从A23187刺激的细胞释放的[3H] AA标记的代谢物的分析表明，过氧化氢对磷脂酶活性没有影响。因此，ROS可刺激或抑制肾小球系膜区AA代谢，在肾小球损伤时可能对肾小球血流动力学有重要影响。
Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, assessed by 51Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E2 (PGE2) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased to 38.1 .+-. 9.7 or 30.8 .+-. 6.9% of control levels (P < 0.05) when cells were stimulated with the calcium ionophore A23187 (1 .mu.g/ml) or AA (10-6 M), respectively. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B2 production was similarly decreased to 83.1 .+-. 7.6 (0.05 < P < 0.10) or 54.9 .+-. 2.5% (P < 0.05). This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H2O2 was the responsible metabolite. High levels of H2O2 (5 .times. 10-4 M) suppressed PGE2 production to 44.0 .+-. 4.1 or 17.4 .+-. 6.2% of A23187- or AA-stimulated production (P < 0.05). Lower levels of H2O2 resulted in significant stimulation of base-line PGE2 production. Analysis of release of [3H]AA-labeled metabolites from A23187-stimulated cells showed no effect of H2O2 on phospholipase activity. Thus ROS can stimulate or inhibit AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury.