Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase
Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase
复制标题
铁通过糖尿病大鼠的氧化/硝化应激增加肝损伤：葡萄糖激酶硝基酪氨酸化的参与
DOI：
10.1016/j.biochi.2012.07.019
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发表时间：
2012-12-01
期刊：
影响因子：
3.9
通讯作者：
Gao, Zhonghong
中科院分区：
文献类型：
--
作者：
Li, Xueli;Li, Hailing;Gao, Zhonghong
过量的组织铁水平与氧化/硝化应激的增加有关，这有助于组织损伤，可能会增加糖尿病的风险。因此，我们研究了铁对糖尿病相关肝损伤的影响，以及铁相关的酪氨酸硝化是否参与了这一过程。将大鼠随机分为4组：对照组、铁负荷组（300 mg/kg右旋糖酐铁，i. p.）、糖尿病患者（在给予高脂肪饮食后腹膜内注射35 mg/kg链脲佐菌素）和同时用铁治疗的糖尿病患者。补铁通过增加肝/体重比、血清天冬氨酸和丙氨酸转氨酶水平以及组织学检查显著增加糖尿病介导的肝损伤和肝功能障碍，这与脂质过氧化、蛋白质羰基化和酪氨酸硝化水平升高、一氧化氮氧化代谢和抗氧化能力降低相关。因此，氧化/硝化葡萄糖激酶的程度显着增加，在铁治疗的糖尿病大鼠，有助于减少其表达和活性。进一步的研究表明，铁诱导的特定葡萄糖激酶硝化位点对其失活有重要贡献。总之，铁促进糖尿病介导的氧化/硝化应激的升高，同时损害肝脏GK，并且可以是酶变化和肝功能障碍之间的联系。这些发现可能为铁在糖尿病发病机制中的作用提供新的见解。(C)2012年Elsevier Masson SAS。All rights reserved.
Excessive tissue iron levels are associated with the increase of oxidative/nitrative stress which contributes to tissue damage that may elevate the risk of diabetes. Therefore, we investigated the effects of iron on diabetes-associated liver injury and whether iron-related tyrosine nitration participated in this process. Rats were randomly divided into four groups: control, iron overload (300 mg/kg iron dextran, i.p.), diabetic (35 mg/kg of streptozotocin i.p. after administration of a high-fat diet) and diabetic simultaneously treated with iron. Iron supplement markedly increased diabetes-mediated liver damage and hepatic dysfunction by increasing liver/body weight ratio, serum levels of aspartate and alanine aminotransferase, and histological examination, which were correlated with elevated levels of lipid peroxidation, protein carbonyls and tyrosine nitration, oxidative metabolism of nitric oxide, and reduced antioxidant capacity. Consequently, the extent of oxidized/nitrated glucokinase was markedly increased in the iron-treated diabetic rats that contribute to a decrease in its expression and activity. Further studies revealed a significant contribution of iron-induced specific glucokinase nitration sites to its inactivation. In conclusion, iron facilitates diabetes-mediated elevation of oxidative/nitrative stress, simultaneously impairs liver GK, and can be a link between enzymatic changes and hepatic dysfunction. These findings may provide new insight on the role of iron in the pathogenesis of diabetes mellitus. (C) 2012 Elsevier Masson SAS. All rights reserved.