Hempel S L, Wessels D A
Department of Veterans Affairs Medical Center, Iowa City, Iowa.
Am J Physiol. 1994 May;266(5 Pt 1):C1392-9. doi: 10.1152/ajpcell.1994.266.5.C1392.
The role of glutathione in protecting prostaglandin (PG) generation after exposure of fibroblasts to oxidant stress was investigated. Exposure of 3T3 fibroblasts to H2O2, followed by washing and then 20 microM arachidonic acid, caused a dose-dependent decrease in PG synthesis as assessed by radioimmunoassay. PGE2 production decreased from 3.7 +/- 1.1 to 0.15 +/- 0.04 pmol/microgram protein, and prostacyclin (PGI2) formation decreased from 0.56 +/- 0.03 to 0.06 +/- 0.03 pmol/microgram protein after exposure to 200 microM H2O2. Decreasing intracellular glutathione with 50 micrograms/ml 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) enhanced the H2O2-induced decrease in PGE2 synthesis. Another glutathione-depleting agent, 1-chloro-2,4-dinitrobenzene (CDNB), also potentiated the H2O2-induced decrease in PGE2 formation. However, although PGI2 production was decreased by H2O2, neither BCNU nor CDNB potentiated this decrease. Without oxidant stress, extreme glutathione depletion decreased PGE2 synthesis and caused PGI2 synthesis to exceed PGE2. In summary, oxidant stress decreases both PGE2 and PGI2 formation. However, the primary effect of decreasing cell glutathione during oxidant stress is a reduction in PGE2 formation, not PGI2. This implies that the predominant effect of glutathione depletion during oxidant stress is on the PGE2 isomerase(s) and not PGH synthase or PGI2 synthase.
研究了谷胱甘肽在成纤维细胞暴露于氧化应激后保护前列腺素（PG）生成中的作用。将3T3成纤维细胞暴露于过氧化氢中，随后洗涤，然后加入20微摩尔花生四烯酸，通过放射免疫测定评估，PG合成呈剂量依赖性下降。暴露于200微摩尔过氧化氢后，前列腺素E2（PGE2）的产生从3.7±1.1皮摩尔/微克蛋白质降至0.15±0.04皮摩尔/微克蛋白质，前列环素（PGI2）的形成从0.56±0.03皮摩尔/微克蛋白质降至0.06±0.03皮摩尔/微克蛋白质。用50微克/毫升1,3-双（氯乙基）-1-亚硝基脲（BCNU）降低细胞内谷胱甘肽水平，增强了过氧化氢诱导的PGE2合成减少。另一种耗竭谷胱甘肽的试剂1-氯-2,4-二硝基苯（CDNB）也增强了过氧化氢诱导的PGE2形成减少。然而，尽管过氧化氢降低了PGI2的产生，但BCNU和CDNB均未增强这种降低作用。在没有氧化应激的情况下，极度的谷胱甘肽耗竭会降低PGE2合成，并导致PGI2合成超过PGE2。总之，氧化应激会降低PGE2和PGI2的形成。然而，在氧化应激期间降低细胞谷胱甘肽的主要作用是减少PGE2的形成，而不是PGI2。这意味着在氧化应激期间谷胱甘肽耗竭的主要作用是作用于PGE2异构酶，而不是PGH合酶或PGI2合酶。
