O2-induced changes in lung and storage pool thiols in mice: effect of superoxide dismutase.
O2-induced changes in lung and storage pool thiols in mice: effect of superoxide dismutase.
复制标题
O2 诱导小鼠肺和储存池硫醇的变化：超氧化物歧化酶的作用。
DOI：
10.1152/jappl.1993.74.3.989
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Stabler,SP
中科院分区：
文献类型：
--
作者：
Rusakow,LS;White,CW;Stabler,SP
由于谷胱甘肽（GSH）是一种重要的抗氧化剂，我们假设，在肺和全身可用性的GSH及其前体氨基酸，半胱氨酸，暴露于高氧诱导的变化，这些变化可以调制的有毒O2代谢产物。在高氧暴露小鼠的器官和血浆中，我们测量了GSH和含硫氨基酸（SAA），后者通过毛细管气相色谱-质谱法。在相对O2耐药性的Swiss-Webster小鼠中，肺GSH在O2暴露期间增加，而肝脏GSH（半胱氨酸的主要储存库）以及肝脏和血浆半胱氨酸均减少。配对喂养研究表明，单独的营养剥夺不会导致血浆半胱氨酸的减少。在肺中，SAA不降低O2暴露。事实上，胱硫醚增加了六倍，γ-胱硫醚酶没有受到抑制。这些结果表明，高氧增加转硫途径的活动和胱硫醚酶速率限制这一进程在肺。在比较研究中，肺GSH增加O2耐高铜锌超氧化物歧化酶（SOD）转基因小鼠，但在遗传相似，非转基因对照（CBYB/6 × B6 D/2）在高氧暴露。此外，肝脏GSH和血浆半胱氨酸在非转基因对照组中下降，但在高SOD小鼠中没有下降，而肺胱硫醚在两组中相似地增加。因此，超氧化物或其次级产物可以调节，至少部分地，半胱氨酸和GSH的变化。尽管如此，无论应变或SOD状态，高氧暴露一贯引起硫醇和SAA的变化，包括增加肺胱硫醚和氧化GSH，表现出这些动态变化和氧化应激之间的强关联。
Because glutathione (GSH) is an important antioxidant, we hypothesized that changes in lung and systemic availability of GSH and its precursor amino acid, cysteine, are induced by exposure to hyperoxia and that these changes could be modulated by toxic O2 metabolites. In organs and plasma of mice exposed to hyperoxia, we measured GSH and sulfur-containing amino acids (SAAs), the latter by capillary gas chromatography-mass spectrometry. In relatively O2-resistant Swiss-Webster mice, lung GSH increased during O2 exposure, whereas liver GSH (the major storage pool of cysteine) and liver and plasma cysteine all decreased. Pair-feeding studies suggested that nutritional deprivation alone did not cause the decrease in plasma cysteine. In lung, SAAs were not decreased by O2 exposure. In fact, cystathionine increased sixfold, and gamma-cystathionase was not inhibited. These findings suggest that hyperoxia increases transsulfuration pathway activity and that cystathionase rate limits this process in lung. In comparative studies, lung GSH increased in O2-resistant high-CuZn superoxide dismutase (SOD) transgenic mice but not in genetically similar, nontransgenic controls (CBYB/6 x B6D/2) during hyperoxic exposure. In addition, liver GSH and plasma cysteine decreased in nontransgenic control but not in high-SOD mice, whereas lung cystathionine increased similarly in both groups. Thus, superoxide or its secondary products can modulate, at least in part, the changes in cysteine and GSH. Nonetheless, regardless of strain or SOD status, hyperoxic exposure consistently caused thiol and SAA changes, including increased lung cystathionine and oxidized GSH, demonstrating a strong association between these dynamic changes and oxidant stress.