Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.

Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.
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DOI:
10.1016/j.niox.2012.04.002
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发表时间:
2012-06-30
期刊:
Nitric oxide : biology and chemistry
影响因子:
--
通讯作者:
Friedman JM
Friedman JM
中科院分区:
其他
文献类型:
--
作者:
Roche CJ;Dantsker D;Alayash AI;Friedman JM

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循环中存在无细胞血红蛋白(Hb)通常被视为一种病理状态,可导致毒性后果。结合珠蛋白(Hp)是一种存在于血浆中的球状蛋白质,它能与Hb四聚体解离产生的αβ二聚体以高亲合力结合,从而帮助清除游离Hb。最近有令人信服的迹象表明,Hp结合的二聚体(Hb-Hp)的氧化还原性质可能发挥更积极的作用,在控制毒性,通过限制潜在的组织损伤所造成的自由基的传播内产生的血红素含有球蛋白链。本研究进一步研究了Hp通过其对亚硝酸盐通过Hp结合αβ Hb二聚体的亚硝酸盐还原酶活性产生一氧化氮(NO)的影响的潜在保护作用。所呈现的结果表明,Hb-Hp复合物中的Hb二聚体具有氧结合、CO重组和光谱性质,这些性质与Hb物种具有类似于但不完全相同的性质的Hb四聚体的R四元状态一致。与这些观察结果一致的是,在相同条件下,Hb-Hp的初始亚硝酸盐还原酶速率约为HbA的十倍。结合早期的Hb-Hp的氧化还原特性的这些结果进行了讨论,限制在循环中的非细胞血红蛋白的病理生理后果。
The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb–Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb–Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb–Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb–Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation.
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