An investigation of hemopexin redox properties by spectroelectrochemistry: biological relevance for heme uptake
An investigation of hemopexin redox properties by spectroelectrochemistry: biological relevance for heme uptake
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DOI：
10.1007/s10534-007-9112-9
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发表时间：
2008-06-01
期刊：
影响因子：
3.5
通讯作者：
Crumbliss, Alvin L.
中科院分区：
文献类型：
--
作者：
Flaherty, Meghan M.;Rish, Kimberley R.;Crumbliss, Alvin L.
血红素（HPX）有两个主要作用：它在体内隔离游离血红素，以防止这部分的毒性作用，这主要是由于血红素催化自由基形成的能力；它在细胞内运输血红素，从而限制其作为病原体铁源的可用性。用光谱电化学方法测定了血红素和中位血红素（mH）与HPX结合时的氧化还原电位。在pH 7.2时，血红素- hpx组件的E-1/2值在45-90 mV范围内，mH-HPX组件的E-1/2值在5-55 mV范围内，这取决于环境电解质的特性。h - hpx的E-1/2值随着pH从7.2到5.5的变化呈现100 mV的正位移，表明存在单质子依赖平衡。血红素- hpx的E（1/2）值在NaCl的作用下比在KCl的作用下更大，说明Na+和低pH（5.5）稳定血红素- hpx。此外，与KCl相比，含氯盐体系电位更低，说明血红素- hpx更容易氧化。这些与铁/铁血红素还原相关的物理性质在结构和生物学上都与HPX释放血红素运输和调节血红素加氧酶表达相关。与此一致的是，当胞内体的酸化被巴霉素阻止时，血红素- hpx诱导的血红素加氧酶-1不再发生。
Hemopexin (HPX) has two principal roles: it sequesters free heme in vivo for the purpose of preventing the toxic effects of this moiety, which is largely due to heme's ability to catalyze free radical formation, and it transports heme intracellularly thus limiting its availability as an iron source for pathogens. Spectroelectrochemistry was used to determine the redox potential for heme and meso-heme (mH) when bound by HPX. At pH 7.2, the heme-HPX assembly exhibits E-1/2 values in the range 45-90 mV and the mH-HPX assembly in the range 5-55 mV, depending on environmental electrolyte identity. The E-1/2 value exhibits a 100 mV positive shift with a change in pH from 7.2 to 5.5 for mH-HPX, suggesting a single proton dependent equilibrium. The E (1/2) values for heme-HPX are more positive in the presence of NaCl than KCl indicating that Na+, as well as low pH (5.5) stabilizes ferro-heme-HPX. Furthermore, comparing KCl with K2HPO4, the chloride salt containing system has a lower potential, indicating that heme-HPX is easier to oxidize. These physical properties related to ferri-/ferro-heme reduction are both structurally and biologically relevant for heme release from HPX for transport and regulation of heme oxygenase expression. Consistent with this, when the acidification of endosomes is prevented by bafilomycin then heme oxygenase-1 induction by heme-HPX no longer occurs.