Fang J, Akaike T, Maeda H
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Apoptosis. 2004 Jan;9(1):27-35. doi: 10.1023/B:APPT.0000012119.83734.4e.
Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. Biliverdin is subsequently reduced to bilirubin by the enzyme biliverdin reductase. Increasing evidence has indicated the critical role of HO-1 in cytoprotection and more diverse biological functions. Induction of HO-1 by various chemical inducers that are primarily cell stress inducers or by HO-1 gene transfection confers a protective capacity to cultured cells as well as to cells in several in vivo animal models. In addition, HO-1-deficient mice exhibit a significant increase in susceptibility to tissue injury. The cytoprotective action of HO-1 seems to be mainly a function of the antiapoptotic effects of the enzyme. HO-1 is believed to exert this antiapoptotic action by multiple mechanisms: (a) decreased intracellular pro-oxidant levels, (b) increased bilirubin levels, and (c) elevated CO production. CO may produce an antiapoptotic effect by inhibiting both expression of p53 and release of mitochondrial cytochrome c. HO-1 may also be a target in antitumor therapy because the growth of most tumors depends on HO-1. Our preliminary studies with an HO inhibitor showed a promising antitumor effect. This preliminary work warrants continued investigation for possible novel anticancer chemotherapy.
血红素加氧酶-1（HO-1）是一种诱导酶，可催化血红素的氧化降解，形成胆绿素、一氧化碳（CO）和游离铁。随后，胆绿素被胆绿素还原酶还原为胆红素。越来越多的证据表明HO-1在细胞保护和更多样化的生物学功能中起着关键作用。通过主要作为细胞应激诱导剂的各种化学诱导剂或通过HO-1基因转染诱导HO-1，赋予培养细胞以及几种体内动物模型中的细胞保护能力。此外，HO-1缺陷小鼠对组织损伤的易感性显著增加。HO-1的细胞保护作用似乎主要是该酶抗凋亡作用的结果。据信HO-1通过多种机制发挥这种抗凋亡作用：（a）细胞内促氧化剂水平降低，（b）胆红素水平升高，以及（c）CO产生增加。CO可能通过抑制p53的表达和线粒体细胞色素c的释放产生抗凋亡作用。HO-1也可能是抗肿瘤治疗的靶点，因为大多数肿瘤的生长依赖于HO-1。我们用HO抑制剂进行的初步研究显示出有希望的抗肿瘤效果。这项初步工作值得继续研究，以探索可能的新型抗癌化疗方法。
