Amelioration of oxidant stress by the defensin lysozyme
Amelioration of oxidant stress by the defensin lysozyme
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DOI：
10.1152/ajpendo.00349.2005
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发表时间：
2006-05-01
影响因子：
5.1
通讯作者：
Vlassara, H
中科院分区：
文献类型：
--
作者：
Liu, HX;Zheng, F;Vlassara, H
活性氧化剂(ROS)是正常代谢的产物，如果它们在病理性的数量上积累，就会引起氧化损伤。溶菌酶(LZ)含有一个18个氨基酸的结构域，可与产生ROS的晚期糖基化终产物(AGE)等试剂结合。我们使用百草枯和过氧化氢作为急性损伤的试剂，使用年龄作为慢性损伤的药物，研究内源性LZ是否影响生理或基线的抗氧化平衡，并提供对急性和慢性氧化损伤的保护。鸡蛋LZ-TG小鼠的血清LZ水平高出三倍，而血清和肝脏中的基线年龄水平降低。这些发现与基线全身性GSH/GSSG比率升高有关。LZ-TG组小鼠肝组织中应激反应基因p66Shc和c-jun的基线水平也较低。在LZ-TG小鼠中，百草枯诱导的严重氧化损伤的存活率增加了两倍。此外，LZ-TG小鼠对AGE诱导的慢性外源性氧化应激(OS)具有抵抗力。肝细胞(Hep G2)与LZ预先孵育可抑制基线时的氧化还原平衡，以及添加百草枯、AGE或H_2O_2后的OS。LZ还以剂量依赖的方式改善百草枯诱导的细胞凋亡，并抑制AGE诱导的Hep G2细胞p66(Shc)表达和c-jun磷酸化。因此，LZ通过抑制ROS生成和OS反应基因的机制，对急性和慢性氧化损伤提供保护。
Reactive oxidant species (ROS), products of normal metabolism, cause oxidant injury if they accumulate in pathological amounts. Lysozyme (LZ) contains an 18-amino acid domain that binds agents such as advanced glycation end products ( AGE) that generate ROS. We examined whether endogenous LZ affected physiological, or baseline, antioxidant balance and provided protection against both acute and chronic oxidant injury, using paraquat and H2O2 as agents of acute injury and AGE for chronic injury. Hen egg LZ-Tg mice had threefold higher serum LZ levels and decreased baseline AGE levels in serum and liver. These findings were linked to an enhanced baseline systemic GSH-to-GSSG ratio. Baseline levels of stress response genes p66Shc and c-Jun were also lower in liver tissue of LZ-Tg mice. Survival from severe oxidant injury induced by paraquat was twofold greater in LZ-Tg mice. In addition, LZ-Tg mice were resistant to chronic exogenous oxidant stress ( OS) induced by AGE administration. Preincubation of hepatocytes (Hep G2) with LZ suppressed redox balance at baseline, as well as OS after added paraquat, AGE, or H2O2. LZ also ameliorated paraquat-enhanced cell apoptosis in a dose-dependent manner and suppressed AGE-induced p66(Shc) expression and c-Jun phosphorylation in Hep G2 cells. Thus LZ provides protection against acute and chronic oxidant injury by mechanisms involving suppression of ROS generation and of OS response genes.