Hydrogen peroxide induces 21-aminosteroid-inhibitable F2-isoprostane production and cytolysis in renal tubular epithelial cells.
Hydrogen peroxide induces 21-aminosteroid-inhibitable F2-isoprostane production and cytolysis in renal tubular epithelial cells.
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过氧化氢诱导肾小管上皮细胞中 21-氨基类固醇抑制的 F2-异前列腺素产生和细胞溶解。
DOI：
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发表时间：
1995
影响因子：
13.6
通讯作者：
J. Roberts
中科院分区：
文献类型：
--
作者：
A. Salahudeen;K. Badr;J. Morrow;J. Roberts
f2 -异前列腺素是新发现的活性氧催化花生四烯酸过氧化产物。将这些前列腺素f2样类前列腺素输注到大鼠肾脏中，可诱导RBF和GFR的显著平行降低，这表明这些代谢物可能是自由基相关性急性肾损伤模型中血流动力学改变的部分原因。本研究直接在肾近端小管（LLC-PK1）细胞中检测过氧化氢（一种涉及许多急性肾损伤模型的活性氧）是否诱导f2 -异前列腺素的产生，以及最近合成的脂质过氧化抑制剂21-氨基类固醇（lazaroid U-74389G）是否可以抑制其产生。lc - pk1细胞层与过氧化氢孵育3小时，通过气相色谱-质谱法测量，f2 -异前列腺素的产量增加了6倍。用21-氨基类固醇预孵生细胞可阻止过氧化氢诱导的f2 -异前列腺素的产生，这一发现也可用于其他脂质过氧化抑制剂，例如2-甲基氨基chroman （U-83836E）和二苯基-对苯二胺。除了抑制异前列腺素的产生外，21-氨基类固醇还能减少过氧化氢诱导的脂质降解和过氧化，并保护细胞免受过氧化氢诱导的细胞溶解。过氧化氢诱导肾上皮细胞产生21-氨基类固醇抑制f2 -异前列腺素的新发现支持了体内报告，即其水平在活性氧相关的肾损伤模型（如缺血-再灌注）中升高。除了直接的细胞损伤外，脂质过氧化产生f2 -异前列腺素可能通过血管收缩机制进一步导致肾功能障碍。因此，抑制过量f2 -异前列腺素的产生可能是除细胞保护外，抗氧化剂改善急性肾损伤实验模型肾功能障碍的另一机制。
F2-isoprostanes are the newly identified reactive oxygen species-catalyzed peroxidation products of arachidonate. The infusion of these prostaglandin F2-like prostanaoids into the rat kidney induces profound parallel reductions in RBF and GFR, suggesting that these metabolites may be partly responsible for the hemodynamic alterations seen in free radical-linked acute renal injury models. The present study examined directly in renal proximal tubular (LLC-PK1) cells whether hydrogen peroxide, a reactive oxygen species implicated in many models of acute renal injury, induces F2-isoprostane production and whether its production can be inhibited by the recently synthesized lipid peroxidation inhibitor 21-aminosteroid (lazaroid U-74389G). The incubation of LLC-PK1 cell layers with hydrogen peroxide for 3 h resulted in a dose-related six-fold increase in F2-isoprostane production, measured by the gas chromatographic-mass spectroscopic method. The preincubation of cells with 21-aminosteroid prevented hydrogen peroxide-induced F2-isoprostane production, a finding also demonstrable with other lipid peroxidation inhibitors, e.g., 2-methyl aminochroman (U-83836E) and diphenyl-p-phenylenediamine. Besides inhibiting isoprostane production, 21-aminosteroid reduced hydrogen peroxide-induced lipid degradation and peroxidation, and protected the cells against hydrogen peroxide-induced cytolysis. The novel finding that hydrogen peroxide induces 21-aminosteroid-inhibitable F2-isoprostane production in renal epithelial cells supports the in vivo report that its levels are elevated in reactive oxygen species-linked renal injury models such as ischemia-reperfusion. Besides direct cell injury, lipid peroxidation by generating F2-isoprostanes may further contribute to renal dysfunction through a vasoconstrictive mechanism. Thus, the inhibition of excess F2-isoprostane production may be one of the additional mechanisms, besides cytoprotection, by which antioxidants ameliorate renal dysfunction in experimental models of acute renal injury.
肾缺血后的氧化应激：谷胱甘肽氧化还原比的变化。
影响因子：
19.6
作者：
McCoy,RN;Hill,KE;Ayon,MA;Stein,JH;Burk,RF
通讯作者：
Burk,RF
影响因子：
15.9
作者：
PALLER, MS;HOIDAL, JR;FERRIS, TF
通讯作者：
FERRIS, TF
DOI：
10.1073/pnas.87.23.9383
发表时间：
1990-12-01
影响因子：
11.1
作者：
MORROW, JD;HILL, KE;ROBERTS, LJ
通讯作者：
ROBERTS, LJ