Ferrándiz M L, Devesa I
Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n 46100 Burjasot, Valencia, Spain.
Curr Pharm Des. 2008;14(5):473-86. doi: 10.2174/138161208783597399.
Heme oxygenase-1 (HO-1) is an inducible rate-limiting enzyme which catalyzes group heme into carbon monoxide, iron and bilirubin. In the recent years, HO-1 expression has been reported as an important protective endogenous mechanism against physical, chemical and biological stress. In this regard, induction of this enzyme has shown beneficial effects in several pathologic conditions, such as inflammatory processes, atherosclerosis, carcinogenesis, ischemia-reperfusion systems or degenerative diseases. Complex intracellular signalling cascades mediate the expression of HO-1 in response to external stimuli, Transcription factors, as nuclear factor E2-related factor-2, activator protein-1, and nuclear factor-kappa B, and some of their upstream kinases, mitogen-activated protein kinases, phosphatidylinositol 3-kinase, or protein kinases A, C are responsible of the HO-1 gene expression. The purpose of this article is to review the increasing number of natural and synthetic molecules reported to induce HO-1 as additive mechanism responsible for their therapeutic effects; experimental and pathological conditions as well as possible signalling mechanism involved in HO-1 expression by this compounds are described. Controlled upregulation of this enzyme, or its catalytic activity, has shown antioxidant, anti-proliferative, anti-apoptotic and anti-inflammatory properties. For this reason, pharmacologic modulation of HO-1 system may represent an effective and cooperative strategy to intervene in several pathologic conditions.
血红素加氧酶-1（HO-1）是一种可诱导的限速酶，它催化血红素基团生成一氧化碳、铁和胆红素。近年来，HO-1的表达被报道为一种重要的内源性保护机制，可抵御物理、化学和生物应激。在这方面，该酶的诱导在多种病理状况下已显示出有益作用，如炎症过程、动脉粥样硬化、致癌作用、缺血再灌注系统或退行性疾病。复杂的细胞内信号级联反应介导HO-1对外界刺激的表达，转录因子，如核因子E2相关因子-2、激活蛋白-1和核因子κB，以及它们的一些上游激酶，丝裂原活化蛋白激酶、磷脂酰肌醇3激酶或蛋白激酶A、C，负责HO-1基因的表达。本文的目的是综述越来越多的天然和合成分子，这些分子被报道可诱导HO-1作为其治疗作用的附加机制；描述了实验和病理状况以及这些化合物参与HO-1表达的可能信号机制。对该酶或其催化活性进行可控的上调已显示出抗氧化、抗增殖、抗凋亡和抗炎特性。因此，对HO-1系统进行药理学调节可能是干预多种病理状况的一种有效且协同的策略。
