Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation
Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation
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DOI：
10.1016/j.thromres.2004.09.011
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发表时间：
2005-01-01
影响因子：
7.5
通讯作者：
Maruyama, I
中科院分区：
文献类型：
--
作者：
Yamaji, K;Wang, Y;Maruyama, I
活性蛋白C（APC）是一种重要的天然抗凝剂，是蛋白水解产生的。通过在内皮表面上存在血栓调节蛋白的情况下调节凝血酶活性而从蛋白C（PC）中分离。近年来的研究表明，APC除了具有抗凝血活性外，还具有抗炎和细胞保护作用，其抗炎作用的机制尚不清楚。方法：我们首先检测了APC对小鼠巨噬细胞样RAW264.7细胞活性氧（ROS）和炎性细胞因子产生的影响。我们进一步研究了APC对化学诱导的脂质过氧化和晚期糖基化终产物（AGE）形成的影响。结果和结论：APC在10-50 μ g/mL的范围内可以减少脂多糖（LPS）诱导的ROS生成，核因子κ B（NF-κ B）激活和由此产生的促炎细胞因子的产生。另外的无细胞实验显示APC（10-50 μ g/mL）对脂质过氧化和AGE形成具有抑制作用。这些研究结果表明，APC，通过其固有的抗氧化特性，可能会在氧化应激的设置，发挥重要的细胞保护和抗炎作用，这是不同于其抗凝活性作为一种抗氧化蛋白。如果这是真的，APC可能有助于ROS相关的慢性疾病，包括动脉粥样硬化和糖尿病以及急性休克状况。(C)2004爱思唯尔有限公司保留所有权利。
Introduction: Activated protein C (APC) is an important natural anticoagulant that is proteolyticatly generated. from protein C (PC) by the modulation of thrombin activity in the, presence of thrombomodulin on an endothelial surface. Recent studies have demonstrated that, beyond its anticoagulant acitivities, APC had anti-inflammatory and cytoprotective properties The mechanisms underlying APC's anti-inflammatory effects remain unknown. Our goat was to elucidate and confirm these mechanisms.Methods: We first examined the effect of APC on reactive oxygen species (ROS) and inflammatory cytokine production in murine macrophage-like RAW264.7 cells. We further examined the effect of APC on chemically induced lipid peroxidation and advanced glycation end-products (AGE) formation.Results and conclusions: APC in the range of 10-50 mug/mL could reduce lipopolysaccharide (LPS)-induced ROS generation, nuclear factor kappaB (NF-kappaB) activation and resultant proinflammatory cytokine production. Additional cell-free experiments revealed that APC (10-50 mug/mL) had inhibitory effects on lipid peroxidation and AGE formation. These findings suggest that APC, via its intrinsic anti-oxidant properties, may, in settings of oxidant stress, exert important cytoprotective and anti-inflammatory effects that are distinct from its anticoagulant activity as an antioxidant protein. If that is true, APC may contribute to ROS-related chronic disorders including atherosclerosis and diabetes as well as acute shock conditions. (C) 2004 Elsevier Ltd. All rights reserved.