de Oliveira Joseana, Denadai Marina B, Costa Diego L
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto 14049-900, Brazil.
Programa de Pós-Graduação em Imunologia Básica e Aplicada, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto 14049-900, Brazil.
Antioxidants (Basel). 2022 Apr 27;11(5):861. doi: 10.3390/antiox11050861.
Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the degradation of heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The anti-inflammatory and antioxidant properties of HO-1 activity are conferred in part by the release of CO and BV and are extensively characterized. However, iron constitutes an important product of HO-1 activity involved in the regulation of several cellular biological processes. The macrophage-mediated recycling of heme molecules, in particular those contained in hemoglobin, constitutes the major mechanism through which living organisms acquire iron. This process is finely regulated by the activities of HO-1 and of the iron exporter protein ferroportin. The expression of both proteins can be induced or suppressed in response to pro- and anti-inflammatory stimuli in macrophages from different tissues, which alters the intracellular iron concentrations of these cells. As we discuss in this review article, changes in intracellular iron levels play important roles in the regulation of cellular oxidation reactions as well as in the transcriptional and translational regulation of the expression of proteins related to inflammation and immune responses, and therefore, iron metabolism represents a potential target for the development of novel therapeutic strategies focused on the modulation of immunity and inflammation.
血红素加氧酶-1（HO-1）是一种催化血红素降解的酶，可释放等摩尔量的一氧化碳（CO）、胆绿素（BV）和铁。HO-1活性的抗炎和抗氧化特性部分归因于CO和BV的释放，并且已得到广泛表征。然而，铁是HO-1活性的重要产物，参与多种细胞生物学过程的调节。巨噬细胞介导的血红素分子循环利用，特别是血红蛋白中所含的血红素分子，是生物体获取铁的主要机制。这一过程受到HO-1和铁输出蛋白铁转运蛋白活性的精细调节。在来自不同组织的巨噬细胞中，这两种蛋白质的表达可根据促炎和抗炎刺激而被诱导或抑制，从而改变这些细胞内的铁浓度。正如我们在这篇综述文章中所讨论的，细胞内铁水平的变化在细胞氧化反应的调节以及与炎症和免疫反应相关蛋白质表达的转录和翻译调节中发挥着重要作用，因此，铁代谢是开发专注于调节免疫和炎症的新型治疗策略的潜在靶点。
