Sulfite species enhance carbon monoxide release from CO-releasing molecules: Implications for the deoxymyoglobin assay of activity
Sulfite species enhance carbon monoxide release from CO-releasing molecules: Implications for the deoxymyoglobin assay of activity
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DOI：
10.1016/j.ab.2012.04.026
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发表时间：
2012-08-01
影响因子：
2.9
通讯作者：
Poole, Robert K.
中科院分区：
文献类型：
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作者：
McLean, Samantha;Mann, Brian E.;Poole, Robert K.
一氧化碳释放分子(CO-RMS)模拟了CO在生物学中的有益(例如，抗炎)作用。CO-RMS的CO释放量通常是通过测量羧基肌红蛋白(Mb-CO)的生成来确定的。以前的研究强调了使用该方法建立的一些CO-RMS的表观CO释放速率与其他实验数据之间的差异，在其他实验数据中，提出了较慢或更复杂的释放机制。有人假设，一些CO-RMS需要一个CO受体，在Mb-CO分析中被认为是还原的肌红蛋白，以促进CO的释放。在这里，我们第一次证明，在只有还原肌红蛋白存在的情况下，基于Ru的[Ru(CO)(3)Cl-2](2)(Corm-2)和[Ru(CO)(3)Cl(甘氨酸)](Corm-3)不能以相当快的速度释放CO。相反，我们确认是还原剂二亚硫酸钠促进了CO从这些CO-RMS中释放出来。其他亚硫酸盐化合物，即亚硫酸钠和焦亚硫酸钾，也促进CO从CORM-3中释放出来。我们描述了一种消除重亚硫酸盐的替代氧合血红蛋白测定方法，并认为CO-RMS的疗效源于细胞内与阴离子的相互作用，从而促进了CO向治疗靶点的输送。(C)2012 Elsevier Inc.保留所有权利。
Carbon monoxide-releasing molecules (CO-RMs) emulate the beneficial (e.g., anti-inflammatory) effects of CO in biology. CO release from CO-RMs is routinely determined in the presence of reduced deoxy-myoglobin by measuring the formation of carboxy-myoglobin (Mb-CO). Previous studies have highlighted discrepancies between the apparent CO release rates of some CO-RMs established using this assay versus other experimental data where a slower or more complex mechanism of release is suggested. It has been hypothesized that some CO-RMs require a CO acceptor, believed to be reduced myoglobin in Mb-CO assays, in order to facilitate the release of CO. Here, we show, for the first time, that CO is not liberated from the ruthenium (Ru)-based [Ru(CO)(3)Cl-2](2) (CORM-2) and [Ru(CO)(3)Cl(glycinate)] (CORM-3) at an appreciable rate in the presence of reduced myoglobin alone. Rather, we confirm that it is the reducing agent sodium dithionite that facilitates release of CO from these CO-RMs. Other sulfite compounds, namely sodium sulfite and potassium metabisulfite, also promote the liberation of CO from CORM-3. We describe an alternative oxy-hemoglobin assay that eliminates dithionite and suggest that the efficacy of CO-RMs results from intracellular interactions with anions that facilitate CO delivery to therapeutic targets. (C) 2012 Elsevier Inc. All rights reserved.