Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin.
Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin.
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DOI：
10.1016/j.freeradbiomed.2014.01.030
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发表时间：
2014-04
影响因子：
7.4
通讯作者：
Alayash, Abdu I.
中科院分区：
文献类型：
--
作者：
Mollan, Todd L.;Jia, Yiping;Banerjee, Sambuddha;Wu, Gang;Kreulen, R. Timothy;Tsai, Ah-Lim;Olson, John S.;Crumbliss, Alvin L.;Alayash, Abdu I.
关键词：
结合珠蛋白(Hp)是一种含量丰富且保守的血浆糖蛋白，它能高亲和力结合无细胞成人血红蛋白(Hb)二聚体，促进其在溶血后迅速清除。人类有三种主要的幽门螺杆菌表型，分别为Hp1-1、Hp2-1和Hp2-2。这些变体表现出不同的结构构型，并已被报道在功能上不对等。我们研究了用商业分离的HP制备的Hb-HP络合物的功能性质和氧化还原性质，发现所有形式的Hb-HP都表现出相似的行为。Hb二聚体与Hp结合的速度与双分子速率常数~0.9μM−1s−1有关，与所检测的Hp类型无关。虽然Hp结合确实通过将Hb四聚体解离成二聚体来加速观察到的HBO2自氧化速度，但这些结合的二聚体的观察到的速度比溶液中没有Hb的二聚体慢3-4倍。Hb铁与任何形式的Hp共同孵育可将血红素损失抑制到检测到的水平以下。每个HB-HP络合物的铁/铁对的本征氧化还原电位(E_1/2)是相似的，从+54 mV到+59 mV(Vs NHE)，与我们以前报道的由普通HP制备的HB-HP络合物基本相同。所有Hb-HP络合物在接触过氧化氢后都会产生类似的高铁Hb。EPR数据表明，在这个过程中，蛋白质基自由基产率约为4%~5%，不受HP变种的影响。这些数据表明，所研究的HP组分在Hb结合以及相关的稳定性和氧化还原特性方面是相同的，这一结果应该被考虑到旨在对抗Hb介导的血管疾病的表型特异性HP疗法的设计中。
Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation following hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally non-equivalent. We have investigated the functional and redox properties of Hb-Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9 μM−1s−1, irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autooxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is 3- to 4-fold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb-Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb-Hp complexes prepared from unfractionated Hp. All Hb-Hp complexes generate similar high amounts of ferryl Hb following exposure to hydrogen peroxide. EPR data indicate that the yields of protein-based radicals during this process are approximately 4% to 5%, and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to each other with respect to Hb binding and associated stability and redox properties, and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease.
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影响因子：
--
作者：
ALLISON, AC;REES, W
通讯作者：
REES, W
DOI：
10.1073/pnas.56.3.974
发表时间：
1966-01-01
影响因子：
11.1
作者：
BUNN, HF;JANDL, JH
通讯作者：
JANDL, JH
DOI：
10.1016/0005-2795(70)90045-0
发表时间：
1970-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALFSON, A;CHIANCONE, E;ANTONINI, E
通讯作者：
ANTONINI, E
影响因子：
6
作者：
Butt, Omer I.;Buehler, Paul W.;D'Agnillo, Felice
通讯作者：
D'Agnillo, Felice
影响因子：
4.1
作者：
CONNELL, GE;SMITHIES, O
通讯作者：
SMITHIES, O