Carbon monoxide-releasing molecules - Characterization of biochemical and vascular activities
Carbon monoxide-releasing molecules - Characterization of biochemical and vascular activities
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DOI：
10.1161/hh0202.104530
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发表时间：
2002-02-08
影响因子：
20.1
通讯作者：
Green, CJ
中科院分区：
文献类型：
--
作者：
Motterlini, R;Clark, JE;Green, CJ
一氧化碳（CO）是在血红素氧合酶降解血红素的过程中在生物体中产生的，血红素氧合酶以组成型（HO-2和HO-3）和诱导型（HO-1）异构体存在。已知一氧化碳气体以类似于一氧化氮的方式扩张血管，并且最近已显示具有抗炎和抗凋亡特性。我们报告了一系列过渡金属羰基化合物，这里称为一氧化碳释放分子（CO-RM），释放CO引起直接的生物活性。具体而言，分光光度法和NMR分析表明，十羰基二锰和三羰基二氯钌（II）二聚体释放CO的浓度依赖性的方式。此外，CO-RM引起持续的血管舒张预收缩大鼠主动脉环，衰减离体心脏冠状动脉血管收缩，并显着降低体内急性高血压。这些血管的影响被模仿诱导HO-1治疗后的动物与氯化血红素，增加内源性产生的CO。因此，我们已经确定了一类新的化合物，是有用的原型用于研究CO的生物活性。在长期内，过渡金属羰基化合物可用于治疗性提供CO，以减轻血管和免疫相关的功能障碍。这篇文章的全文可以在http://www.circresaha.org上找到。
Carbon monoxide (CO) is generated in living organisms during the degradation of heme by the enzyme heme oxygenase, which exists in constitutive (HO-2 and HO-3) and inducible (HO-1) isoforms. Carbon monoxide gas is known to dilate blood vessels in a manner similar to nitric oxide and has been recently shown to possess anti inflammatory and antiapoptotic properties. We report that a series of transition metal carbonyls, termed here carbon monoxide-releasing molecules (CO-RMs), liberate CO to elicit direct biological activities. Specifically, spectrophotometric and NMR analysis revealed that dimanganese decacarbonyl and tricarbonyldichlororuthenium (II) dimer release CO in a concentration-dependent manner. Moreover, CO-RMs caused sustained vasodilation in precontracted rat aortic rings, attenuated coronary vasoconstriction in hearts ex vivo, and significantly reduced acute hypertension in vivo. These vascular effects were mimicked by induction of HO-1 after treatment of animals with hemin, which increases endogenously generated CO. Thus, we have identified a novel class of compounds that are useful as prototypes for studying the bioactivity of CO. In the long term, transition metal carbonyls could be utilized for the therapeutic delivery of CO to alleviate vascular- and immuno-related dysfunctions. The full text of this article is available at http://www.circresaha.org.