Oxidation of Plasma Cysteine/Cystine Redox State in Endotoxin-Induced Lung Injury
Oxidation of Plasma Cysteine/Cystine Redox State in Endotoxin-Induced Lung Injury
复制标题
DOI：
10.1165/rcmb.2007-0447oc
复制
发表时间：
2009-01-01
影响因子：
6.4
通讯作者：
Rojas, Mauricio
中科院分区：
文献类型：
--
作者：
Iyer, Smita S.;Jones, Dean P.;Rojas, Mauricio
一些证据表明，细胞外硫醇/二硫化物氧化还原环境的扰动与急性肺损伤（ALI）的进展和严重程度相关。半胱氨酸（Cys）及其二硫半胱氨酸（CySS）构成了血浆中含量最丰富、低分子量的硫醇/二硫氧化还原对，在感染和损伤的炎症反应中，Cys的稳态受到不利影响。虽然很多的重点放在谷胱甘肽（GSH）和谷胱甘肽二硫（GSSG）上，但很少有人知道Cys/CySS对ALI的调节。本研究的目的是确定给药是否会导致Cys减少和/或血浆Cys/CySS氧化还原状态（E-h Cys/CySS）的氧化，并确定这些变化是否与血浆E-h GSH/GSSG的变化有关。小鼠腹腔注射内毒素，在已知与内毒素诱导的肺损伤进展相关的时间点测量GSH和Cys氧化还原状态。利用高效液相色谱法和能思特方程，利用Cys、CySS、GSH和GSSG值计算mV中的E-h。在急性期，我们观察到封闭毒素对GSH和Cys氧化还原系统的明显影响；血浆E-h GSH/ CySS在早期被选择性氧化，而Eh GSH/GSSG保持不变。出乎意料的是，由于内毒素引起的厌食症，Eh GSH/GSSG和Eh Cys/CySS随后发生氧化。综上所述，内毒素血症中Cys氧化增强、Cys和CySS转运改变以及食物摄入减少均有助于血浆Cys/CySS氧化还原状态的氧化。
Several lines of evidence indicate that perturbations in the extracellular thiol/disulfide redox environment correlate with the progression and severity of acute lung injury (ALI). Cysteine (Cys) and its disulfide Cystine (CySS) constitute the most abundant, low-molecular-weight thiol/disulfide redox couple in the plasma, and Cys homeostasis is adversely affected during the inflammatory response to infection and injury. While much emphasis has been placed on glutathione (GSH) and glutathione disulfide (GSSG), little is known about the regulation of the Cys/CySS couple in ALI. The purpose of the present study was to determine whether enclotoxin administration causes a decrease in Cys and/or an oxidation of the plasma Cys/CySS redox state (E-h Cys/CySS), and to determine whether these changes were associated with changes in plasma E-h GSH/GSSG. Mice received enclotoxin intraperitoneally, and GSH and Cys redox states were measured at time points known to correlate with the progression of endotoxin-induced lung injury. E-h in mV was calculated using Cys, CySS, GSH, and GSSG values by high-performance liquid chromatography and the Nernst equation. We observed distinct effects of enclotoxin on the GSH and Cys redox systems during the acute phase; plasma E-h Cys/CySS was selectively oxidized early in response to enclotoxin, while Eh GSH/GSSG remained unchanged. Unexpectedly, subsequent oxidation of Eh GSH/GSSG and Eh Cys/CySS occurred as a consequence of endotoxin-induced anorexia. Taken together, the results indicate that enhanced oxidation of Cys, altered transport of Cys and CySS, and decreased food intake each contribute to the oxidation of plasma Cys/CySS redox state in endotoxemia.