Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis: An expanded view of the stress response
Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis: An expanded view of the stress response
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DOI：
10.1046/j.1471-4159.2000.0752555.x
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发表时间：
2000-12-01
影响因子：
4.7
通讯作者：
LeVine, SM
中科院分区：
文献类型：
--
作者：
Emerson, MR;LeVine, SM
氧化应激与实验性过敏性脑脊髓炎 (EAE) 的发病机制有关，EAE 是一种多发性硬化症模型，血红素加氧酶-` (HO-1) 是一种由氧化应激诱导的热休克蛋白。 HO-1 将促氧化血红素代谢为抗氧化剂胆绿素和 CO。HO-1 需要电子（由 NADPH 细胞色素 P450 还原酶（以下称为还原酶）提供）来发挥催化活性。用蛋白脂蛋白肽诱导SJL小鼠EAE，并分析后脑中HO-1和还原酶的表达。与对照小鼠相比，EAE 动物中的 HO-1 蛋白水平显着增加。 HO-1 表达存在于白质轨道中的阿米巴巨噬细胞、反应性小胶质细胞和星形胶质细胞中。伯格曼神经胶质细胞和阿米巴巨噬细胞偶尔也会在小脑的分子层中被染色。与 HO-1 不同，还原酶蛋白水平随着疾病严重程度而降低。 HO-1和还原酶在内质网胶束中相互关联，表明还原酶的减少不会干扰其与HO-1的关联。在表达 HO-1 的细胞中，还原酶与 HO-1 的结合应竞争性抑制还原酶与细胞色素 P450 同工酶的相互作用，从而限制自由基的产生，因为后两种酶协同作用产生超氧化物。 HO-1 的增加和还原酶的减少可能是一种常见防御机制的一部分，试图在几种神经系统疾病中尽量减少组织损伤。
Oxidative stress is implicated in the pathogenesis of experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis, Heme oxygenase-` (HO-1) is a heat shock protein induced by oxidative stress. HO-1 metabolizes the pro-oxidant heme to the antioxidant biliverdin and CO. HO-1 requires electrons, donated by NADPH cytochrome P450 reductase thenceforth, reductase), for catalytic activity. EAE was induced with a peptide of proteolipid protein in SJL mice, and the expression of HO-1 and reductase in the hindbrain was analyzed. HO-1 protein levels were significantly increased in EAE animals compared with control mice. HO-1 expression was present in ameboid macrophages, reactive microglia, and astrocytes in white matter tracks. Bergmann glia and ameboid macrophages also were occasionally stained in the molecular layer of the cerebellum. Unlike HO-1, reductase protein levels decreased with disease severity. HO-1 and reductase were associated with each other in endoplasmic reticulum micelles, suggesting that the decrease in reductase does not interfere with its association with HO-1. In cells that express HO-1, the association of reductase with HO-1 should competitively inhibit the interaction of reductase with cytochrome P450 isozymes and thereby limit free radical production as the latter two enzymes act cooperatively to produce superoxide. The increase in HO-1 together with the decrease in reductase may be part of a common defense mechanism attempting to minimize tissue damage in several neurological conditions.