Protection against iron- and hydrogen peroxide-dependent cell injuries by a novel synthetic iron catalase mimic and its precursor, the iron-free ligand
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- 作者：Rauen ; Ursula ; Li ; Tongju ; Sustmann ; Reiner ; de Groot ; Herbert
- 关键词：DMSO ; dimethyl sulfoxide ; Fe/8-HQ ; iron(III)/8-hydroxyquinoline (1 ; 2) ; GOD ; glucose oxidase ; HBSS ; Hanks?????? balanced salt solution ; HTK solution ; histidine??????tryptophan??????ketoglutarate solution ; KH buffer ; Krebs??????Hense
- 刊名：Free Radical Biology and Medicine
- 出版年：2004
- 出版时间：November 1, 2004
- 年：2004
- 卷：37
- 期：9
- 页码：1369-1383
- 全文大小：718 K
文摘
Hydrogen peroxide is involved in many types of cell injury and exerts most of its injurious effects in conjunction with chelatable iron. We previously described a synthetic nonporphyrin iron-containing catalase mimic, TAA-1/Fe. Its ligand TAA-1 was designed for application in biological systems in which it is supposed to fulfill a dual task: it should chelate cellular labile iron and thus form the active catalase mimic, thereby decreasing levels of redox-active iron and enhancing the degradation of hydrogen peroxide. Here, we tested these novel compounds in cellular systems, i.e., in cultured hepatocytes and liver endothelial cells. Both the iron complex, i.e., the complete mimic, and the ligand, i.e., the putative precursor of this mimic, provided protection against endothelial cell injury induced by exogenous hydrogen peroxide. Furthermore, the ligandaaabut not (or less so) the complexaaastrongly protected both cell types against iron-dependent hypothermic injury and hepatocytes against iron-induced cell injury and against iron-dependent, histidine-induced injury. Together, these results demonstrate that the putative catalase mimic precursor TAA-1 is able to protect cells against iron- and/or hydrogen peroxide-dependent cell injuries and thataaain line with our initial conceptaaait is likely to exert its protection by both iron chelation and hydrogen peroxide degradation.