Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes.
Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes.
复制标题
DOI：
10.1016/j.redox.2017.08.008
复制
发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Feinstein SI
中科院分区：
文献类型：
--
作者：
Fisher AB;Vasquez-Medina JP;Dodia C;Sorokina EM;Tao JQ;Feinstein SI
虽然与氧化应激相关的脂质过氧化可导致细胞死亡，但亚致死脂质过氧化可随着恢复到暴露前状态而逐渐消退。我们已经证明，肺或细胞中过氧化物还蛋白6 （Prdx6）的溶解被大大延迟，并且磷脂酶A2和GSH过氧化物酶Prdx6的活性都是最大恢复速率所必需的。与其他过氧化物还毒素一样，Prdx6可以还原H2O2和短链氢过氧化物，但也可以直接还原磷脂氢过氧化物。本研究评估了Prdx6这两种不同的过氧化物酶活性在过氧化细胞膜修复中的相对作用。Prdx6中的His26残基是磷脂结合位点的重要组成部分。因此，我们评估了表达H26A-Prdx6的小鼠的肺部，并通过慢病毒感染Prdx6空细胞生成表达H26A-Prdx6的肺微血管内皮细胞（PMVEC），比较其与野生型对脂质过氧化的修复作用。分离的肺和PMVEC暴露于过氧化叔丁基，小鼠暴露于高氧（> 95% O2）。野生型对照和突变型肺和细胞的脂质过氧化测定显示，在最终暴露时增加了约4倍。对照肺和细胞在暴露后恢复期逐渐消退。然而，H26A-Prdx6肺或PMVEC没有从脂质过氧化中恢复。这些研究证实了Prdx6在膜脂过氧化恢复中的重要作用，并表明H2O2或短链氢过氧化物的还原在恢复过程中不起作用。结论：Prdx6的3种酶活性均参与逆转细胞膜磷脂过氧化作用。过氧化脂质修复在H26A-Prdx6突变中没有发生。修复反应Prdx6的磷脂过氧化物酶和PLA2活性；“P”过氧化物酶活性与小氢过氧化物和H2O2不起修复作用。
Although lipid peroxidation associated with oxidative stress can result in cellular death, sub-lethal lipid peroxidation can gradually resolve with return to the pre-exposure state. We have shown that resolution of lipid peroxidation is greatly delayed in lungs or cells that are null for peroxiredoxin 6 (Prdx6) and that both the phospholipase A2 and the GSH peroxidase activities of Prdx6 are required for a maximal rate of recovery. Like other peroxiredoxins, Prdx6 can reduce H2O2 and short chain hydroperoxides, but in addition can directly reduce phospholipid hydroperoxides. This study evaluated the relative role of these two different peroxidase activities of Prdx6 in the repair of peroxidized cell membranes. The His26 residue in Prdx6 is an important component of the binding site for phospholipids. Thus, we evaluated the lungs from H26A-Prdx6 expressing mice and generated H26A-Prdx6 expressing pulmonary microvascular endothelial cells (PMVEC) by lentiviral infection of Prdx6 null cells to compare with wild type in the repair of lipid peroxidation. Isolated lungs and PMVEC were exposed to tert-butyl hydroperoxide and mice were exposed to hyperoxia (> 95% O2). Assays for lipid peroxidation in wild type control and mutant lungs and cells showed ~4-fold increase at end-exposure. Control lungs and cells showed gradual resolution during a post-exposure recovery period. However, there was no recovery from lipid peroxidation by H26A-Prdx6 lungs or PMVEC. These studies confirm an important role for Prdx6 in recovery from membrane lipid peroxidation and indicate that reduction of H2O2 or short chain hydroperoxides does not play a role in the recovery process. Conclusion: all 3 enzymatic activities of Prdx6 contribute to the reversal of cell membrane phospholipid peroxidation. Repair of peroxidized lipids did not occur with H26A-Prdx6 Delete semicolons;mutation. Repair reflects the phospholipid hydroperoxidase and PLA2 activities of Prdx6;Move to next with "bullet mark" "P"eroxidase activity with small hydroperoxides and H2O2 does not play a role in repair.
登录
查看更多内容
影响因子：
3.9
作者：
Manevich Y;Shuvaeva T;Dodia C;Kazi A;Feinstein SI;Fisher AB
通讯作者：
Fisher AB
影响因子：
--
作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
3.5
作者：
Okimoto, Y;Watanabe, A;Noguchi, N
通讯作者：
Noguchi, N
影响因子：
3.9
作者：
SEVANIAN, A;MUAKKASSAHKELLY, SF;MONTESTRUQUE, S
通讯作者：
MONTESTRUQUE, S
DOI：
10.1073/pnas.182384499
发表时间：
2002-09-03
影响因子：
11.1
作者：
Manevich, Y;Sweitzer, T;Fisher, AB
通讯作者：
Fisher, AB