Vanella Luca, Barbagallo Ignazio, Tibullo Daniele, Forte Stefano, Zappalà Agata, Li Volti Giovanni
Department of Drug Sciences, University of Catania, Catania, Italy.
Division of Haematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
Oncotarget. 2016 Oct 18;7(42):69075-69086. doi: 10.18632/oncotarget.11923.
Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin with a concurrent release of iron, which can drive the synthesis of ferritin for iron sequestration. Most of the studies so far were directed at evaluating the protective effect of these enzymes because of their ability to generate antioxidant and antiapoptotic molecules such as CO and bilirubin. Recent evidences are suggesting that HO may possess other important physiological functions, which are not related to its enzymatic activity and for which we would like to introduce for the first time the term "non canonical functions". Recent evidence suggest that both HO isoforms may form protein-protein interactions (i.e. cytochrome P450, adiponectin, CD91) thus serving as chaperone-like protein. In addition, truncated HO-1 isoform was localized in the nuclear compartment under certain experimental conditions (i.e. excitotoxicity, hypoxia) regulating the activity of important nuclear transcription factors (i.e. Nrf2) and DNA repair. In the present review, we discuss three potential signaling mechanisms that we refer to as the non-canonical functions of the HO isoforms: protein-protein interaction, intracellular compartmentalization, and extracellular secretion. The aim of the present review is to describe each of this mechanism and all the aspects warranting additional studies in order to unravel all the functions of the HO system.
血红素加氧酶（HO）同工型催化血红素转化为一氧化碳（CO）和胆绿素，并同时释放铁，这可以驱动铁螯合蛋白铁蛋白的合成。由于这些酶能够产生抗氧化和抗凋亡分子，如CO和胆红素，迄今为止的大多数研究都致力于评估它们的保护作用。最近有证据表明，HO可能具有其他重要的生理功能，这些功能与其酶活性无关，我们首次引入“非经典功能”这一术语来描述这些功能。最近的证据表明，两种HO同工型都可能形成蛋白质-蛋白质相互作用（即细胞色素P450、脂联素、CD91），从而作为伴侣样蛋白发挥作用。此外，在某些实验条件下（即兴奋性毒性、缺氧），截短的HO-1同工型定位于核区室，调节重要的核转录因子（即Nrf2）的活性和DNA修复。在本综述中，我们讨论了三种潜在的信号传导机制，我们将其称为HO同工型的非经典功能：蛋白质-蛋白质相互作用、细胞内区室化和细胞外分泌。本综述的目的是描述每种机制以及所有需要进一步研究的方面，以便阐明HO系统的所有功能。
