Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury.
Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury.
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DOI：
10.1073/pnas.95.9.5263
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发表时间：
1998-04
影响因子：
11.1
通讯作者：
L. Horwitz;N. A. Sherman;Y. Kong;A. Pike;J. Gobin;P. Fennessey;M. Horwitz
中科院分区：
文献类型：
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作者：
L. Horwitz;N. A. Sherman;Y. Kong;A. Pike;J. Gobin;P. Fennessey;M. Horwitz
再灌注损伤发生在血流重新进入缺血器官时，在心脏病发作和中风中造成相当大的损害。然而，目前还没有治疗再灌注损伤的方法。再灌注损伤的一个主要原因是铁介导的羟基自由基（. oh）的产生。在这项研究中，我们探索了新型铁螯合剂“外螯合剂”防止再灌注损伤的能力。外螯素，结核分枝杆菌的铁载体，是独特的铁螯合剂，因为它们是脂溶性的，因此能够迅速进入细胞。在无铁状态下，外螯素阻止。哦的形成。Desferri-exochelins能比非脂溶性铁螯合剂去铁胺更快速有效地预防培养心肌细胞的氧化损伤。各种铁外螯合蛋白保护肌细胞免受氧化损伤的能力与其在脂质中的溶解度直接相关。在离体家兔心脏缺血再灌注时输注地铁-外chelins可显著改善左心室收缩和舒张功能，保持冠状动脉血流，减少心肌酶乳酸脱氢酶的释放，降低心肌浓度。哦,代谢物。因此，高度扩散的铁外螯合蛋白阻断了。OH的产生和再灌注损伤的治疗潜力。
Reperfusion injury, which occurs upon the reintroduction of blood flow to an ischemic organ, is responsible for considerable damage in heart attacks and strokes. However, no treatment for reperfusion injury is currently available. A major cause of reperfusion injury is the iron-mediated generation of hydroxyl radical (.OH). In this study we have explored the capacity of novel iron chelators called "exochelins" to prevent reperfusion injury. Exochelins, siderophores of Mycobacterium tuberculosis, are unique iron chelators because they are lipid soluble, and hence able to enter cells rapidly. In the iron-free state, exochelins prevented .OH formation. Desferri-exochelins prevented oxidative injury to cultured cardiac myocytes, and did so more rapidly and effectively than the nonlipid soluble iron chelator deferoxamine. The capacity of various desferri-exochelins to protect myocytes from oxidative injury varied directly with their solubility in lipid. Infused into isolated rabbit hearts during reperfusion after a period of ischemia, desferri-exochelins dramatically improved systolic and diastolic left ventricular function, preserved coronary flow, reduced release of the cardiac enzyme lactic dehydrogenase, and reduced myocardial concentrations of .OH metabolites. Thus, highly diffusible desferri-exochelins block injury caused by .OH production and have potential for the treatment of reperfusion injury.