Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivo.
Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivo.
复制标题
红细胞和体内血管室中血红蛋白β93半胱氨酸残基的抗氧化功能。
DOI：
10.1016/j.freeradbiomed.2012.11.003
复制
发表时间：
2013
影响因子：
7.4
通讯作者：
Patel,RakeshP
中科院分区：
文献类型：
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作者：
Vitturi,DarioA;Sun,Chiao-Wang;Harper,VictoriaM;Thrash-Williams,Bessy;Cantu-Medellin,Nadiezhda;Chacko,BaluK;Peng,Ning;Dai,Yanying;Wyss,JMichael;Townes,Tim;Patel,RakeshP
血红蛋白的β93半胱氨酸（β 93 Cys）残基在脊椎动物中是保守的，但其在红细胞（RBC）中的功能尚不清楚。由于该残留物的浓度比RBC抗氧化剂网络的酶组分高2个数量级以上，因此假设其在清除活性物质中发挥作用。利用表达人血红蛋白（在β93位具有Cys（B 93 C）或Ala（B 93 A））的小鼠进行的初步研究表明，β 93 Cys的缺失不会影响RBC抗氧化网络中已建立组分（过氧化氢酶、超氧化物歧化酶、过氧化物氧还蛋白-2、谷胱甘肽过氧化物酶、GSH：GSSG比值）的活性或表达。有趣的是，向RBC中外源性添加参与血管炎症的反应性物质证明了β 93 Cys在过氧化氢和氯胺消耗中的作用。为了模拟体内氧化应激和炎症，用脂多糖（LPS）攻击小鼠。值得注意的是，LPS在B 93 A小鼠中诱导的低血压和肺损伤程度高于B 93 C小鼠，这与RBC反应性物质的形成和肺中DMPO反应性表位的积累有关。这些数据表明，β 93 Cys是RBC抗氧化网络中的重要效应子，有助于调节血管炎症期间的组织损伤。
The β93 cysteine (β93Cys) residue of hemoglobin is conserved in vertebrates but its function in the red blood cell (RBC) remains unclear. Because this residue is present at concentrations more than 2 orders of magnitude higher than enzymatic components of the RBC antioxidant network, a role in the scavenging of reactive species was hypothesized. Initial studies utilizing mice that express human hemoglobin with either Cys (B93C) or Ala (B93A) at the β93 position demonstrated that loss of the β93Cys did not affect activities nor expression of established components of the RBC antioxidant network (catalase, superoxide dismutase, peroxiredoxin-2, glutathione peroxidase, GSH:GSSG ratios). Interestingly, exogenous addition to RBCs of reactive species that are involved in vascular inflammation demonstrated a role for the β93Cys in hydrogen peroxide and chloramine consumption. To simulate oxidative stress and inflammation in vivo, mice were challenged with lipopolysaccharide (LPS). Notably, LPS induced a greater degree of hypotension and lung injury in B93A versus B93C mice, which was associated with greater formation of RBC reactive species and accumulation of DMPO-reactive epitopes in the lung. These data suggest that the β93Cys is an important effector within the RBC antioxidant network, contributing to the modulation of tissue injury during vascular inflammation.