Wagener Frank A D T G, Volk Hans-Dieter, Willis Dean, Abraham Nader G, Soares Miguel P, Adema Gosse J, Figdor Carl G
Department of Tumor Immunology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Pharmacol Rev. 2003 Sep;55(3):551-71. doi: 10.1124/pr.55.3.5. Epub 2003 Jul 17.
The heme-heme oxygenase system has recently been recognized to possess important regulatory properties. It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection, apoptosis, and inflammation. Heme functions as a double-edged sword. In moderate quantities and bound to protein, it forms an essential element for various biological processes, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. The effect of this free heme on the vascular system is determined by extracellular factors, such as hemoglobin/heme-binding proteins, haptoglobin, albumin, and hemopexin, and intracellular factors, including heme oxygenases and ferritin. Heme oxygenase (HO) enzyme activity results in the degradation of heme and the production of iron, carbon monoxide, and biliverdin. All these heme-degradation products are potentially toxic, but may also provide strong cytoprotection, depending on the generated amounts and the microenvironment. Pre-induction of HO activity has been demonstrated to ameliorate inflammation and mediate potent resistance to oxidative injury. A better understanding of the complex heme-heme
血红素-血红素加氧酶系统最近被认为具有重要的调节特性。它紧密参与生理以及病理生理过程，如细胞保护、细胞凋亡和炎症。血红素起着双刃剑的作用。适量且与蛋白质结合时，它是各种生物过程的必需元素，但大量释放时，它可通过介导氧化应激和炎症而变得有毒。这种游离血红素对血管系统的影响由细胞外因素决定，如血红蛋白/血红素结合蛋白、触珠蛋白、白蛋白和血红素结合蛋白，以及细胞内因素，包括血红素加氧酶和铁蛋白。血红素加氧酶（HO）的酶活性导致血红素降解并产生铁、一氧化碳和胆绿素。所有这些血红素降解产物都有潜在毒性，但根据产生的量和微环境，也可能提供强大的细胞保护作用。已证明预先诱导HO活性可减轻炎症并介导对氧化损伤的强大抵抗力。对复杂的血红素-血红素的更好理解
