Heme oxygenase in neuroprotection: from mechanisms to therapeutic implications
Heme oxygenase in neuroprotection: from mechanisms to therapeutic implications
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DOI：
10.1515/revneuro-2013-0046
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发表时间：
2014-04-01
影响因子：
4.1
通讯作者：
Chen, Jijun
中科院分区：
文献类型：
--
作者：
Chen, Jijun
血红素加氧酶（HO）被认为是一种降解老化红细胞中血红素的酶；最近的研究表明 H2O 可能还有其他功能，例如神经保护。 H2O 降解血红素，产生一氧化碳 (CO)、铁 (Fe2+) 和胆绿素，胆绿素迅速转化为胆红素 (BR)。在大脑中鉴定出三种 HO 亚型：诱导型 (HO-1) 和组成型 (HO-2 和 HO-3)。 HO-1和HO-2可能具有不同的机制来保护神经元免受氧化应激。 HO-1 通常在大脑中几乎检测不到。 HO-1主要在小胶质细胞和星形胶质细胞中通过氧化刺激被快速诱导。 HO-1可能作为一种新兴分子来保护神经元免受应激条件下铁从细胞中流出介导的急性损伤。在衰老和神经退行性疾病的脑胶质细胞中也发现了 HO-1 的上调。这可能导致铁沉积和线粒体氧化损伤。由于血红素和血红素产品的有益作用和毒性作用之间的平衡，HO-1 可能具有神经保护作用或神经毒性作用。 HO-1 诱导的药理学调节代表了多种神经系统疾病的治疗策略。 HO-2主要在神经元中表达。胆红素已被证明可以在体内和体外保护神经元免受氧化应激。胆红素可通过清除过氧自由基而氧化为胆绿素。 HO-2可以通过胆红素途径保护神经元。 HO-2 还可能通过 CO-cGMP-MAPK 途径促进神经元存活。胆绿素/胆红素可能是治疗与氧化损伤相关的神经系统疾病的候选药物。
Heme oxygenase (HO) was regarded as an enzyme to degrade heme in aging red blood cells; recent studies suggested HO might have other functions such as neuroprotection. HO degrades heme to produce carbon monoxide (CO), iron (Fe2+) and biliverdin, which is rapidly converted to bilirubin (BR). Three isoforms of HO were identified in the brain: inducible form (HO-1) and constitutive forms (HO-2 and HO-3). HO-1 and HO-2 may have different mechanisms to protect neurons from oxidative stress. HO-1 is normally barely detectable in the brain. HO-1 can be induced mainly in microglia and astrocytes by oxidative stimulus rapidly. HO-1 might function as an emerging molecule to protect neurons against acute insults mediated by facilitating iron efflux from cells under stress conditions. Up-regulation of HO-1 was also found in brain glial cells in the aging and neurodegenerative diseases. This may lead to iron deposition and oxidative mitochondrial injury. HO-1 may confer neuroprotection or neurotoxic effect because of the balance between beneficial and toxic effects of heme and heme products. Pharmacological modulation of HO-1 induction represents a therapeutic strategy for several nervous system disorders. HO-2 predominantly expressed in neurons. Bilirubin has been demonstrated to protect neurons from oxidative stress in vivo and in vitro. Bilirubin can be oxidized to biliverdin by scavenging peroxyl radicals. HO-2 could protect neurons through bilirubin pathway. HO-2 might also promote neuronal survival through the CO-cGMP-MAPK pathway. Biliverdin/bilirubin may be possible therapeutic candidates to treat nervous system disease related with oxidative damage.