Mancuso Cesare, Perluigi Marzia, Cini Chiara, De Marco Carlo, Giuffrida Stella Anna Maria, Calabrese Vittorio
Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
J Neurosci Res. 2006 Nov 15;84(7):1385-91. doi: 10.1002/jnr.21049.
Heme oxygenase (HO) and cyclooxygenase (COX) are two hemeproteins involved in the regulation of several functions in the nervous system. Heme oxygenase is the enzyme responsible for the degradation of heme into ferrous iron, carbon monoxide (CO), and biliverdin, the latter being further reduced in bilirubin (BR) by biliverdin reductase. Heme oxygenase-derived CO is a gaseous neuromodulator and plays an important role in the synaptic plasticity, learning and memory processes, as well as in the regulation of hypothalamic neuropeptide release, whereas BR is an endogenous molecules with antioxidant and anti-nitrosative activities. Cyclooxygenase is considered a pro-inflammatory enzyme as free radicals and prostaglandins (PGs) are produced during its catalytic cycle. Although PGs are also involved in a variety of physiologic conditions including angiogenesis, hemostasis, or regulation of kidney function, upregulation of COX and increase in PGs levels are a common feature of neuroinflammation. In the brain, a functional interplay exists between HO and COX. Heme oxygenase regulates COX activity by reducing the intracellular heme content or by generating CO, which stimulates PGE(2) release. Increased levels of PGs, free radicals, and the associated oxidative stress serve in the brain as a trigger for the induction of HO isoforms which increases cellular antioxidant defenses to counteract oxidative damage. The importance of the interaction between HO and COX in the regulation of physiologic brain functions, and its relevance to neuroprotective or neurodegenerative mechanisms are discussed.
血红素加氧酶（HO）和环氧化酶（COX）是两种参与调节神经系统多种功能的血红素蛋白。血红素加氧酶是一种负责将血红素降解为亚铁离子、一氧化碳（CO）和胆绿素的酶，后者再由胆绿素还原酶进一步还原为胆红素（BR）。血红素加氧酶衍生的CO是一种气态神经调节剂，在突触可塑性、学习和记忆过程以及下丘脑神经肽释放的调节中发挥重要作用，而BR是一种具有抗氧化和抗亚硝化活性的内源性分子。环氧化酶被认为是一种促炎酶，因为在其催化循环中会产生自由基和前列腺素（PGs）。尽管PGs也参与包括血管生成、止血或肾功能调节在内的多种生理状况，但COX的上调和PGs水平的增加是神经炎症的一个共同特征。在大脑中，HO和COX之间存在功能相互作用。血红素加氧酶通过降低细胞内血红素含量或生成CO来调节COX活性，CO会刺激PGE(2)释放。PGs、自由基水平的升高以及相关的氧化应激在大脑中作为诱导HO同工型的触发因素，从而增强细胞抗氧化防御以抵消氧化损伤。本文讨论了HO和COX之间的相互作用在调节生理性脑功能中的重要性及其与神经保护或神经退行性机制的相关性。
