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从髓过氧化物酶遗传性缺乏症看其生物合成机制

Insights into myeloperoxidase biosynthesis from its inherited deficiency.

作者信息

Nauseef W M

机构信息

Department of Medicine, University of Iowa and Veterans Administration Medical Center, Iowa City 52242, USA.

出版信息

J Mol Med (Berl). 1998 Sep;76(10):661-8. doi: 10.1007/s001090050265.

DOI:10.1007/s001090050265
PMID:9766843
Abstract

Myeloperoxidase (MPO) is a heme protein present in the granules of neutrophils and monocytes. The activated neutrophil releases MPO into the phagolysosome or into the extracellular space in response to a variety of agonists. During concomitant activation of the NADPH-dependent oxidase, the stimulated neutrophil also generates hydrogen peroxide, and in this way the MPO-hydrogen peroxide-halide system exerts its potent microbicidal activity. Recent interest in MPO has extended well beyond the domain of innate host defense against infection and includes generalized inflammatory diseases, atherosclerosis, and degenerative neurologic diseases. Search of the various data banks using the cDNA sequence for MPO has uncovered previously unsuspected relationships among peroxidatively active proteins in widely different species. In addition, application of the analytical tools of cell and molecular biology has allowed definition of specific genotypes underlying MPO deficiency and the impact of particular mutations on the fate of MPO precursors along the biosynthetic pathway. In parallel, such studies have allowed significant advances in understanding of the normal steps in MPO biosynthesis and intracellular targeting.

摘要

髓过氧化物酶(MPO)是一种存在于中性粒细胞和单核细胞颗粒中的血红素蛋白。活化的中性粒细胞会响应多种激动剂,将MPO释放到吞噬溶酶体或细胞外空间。在NADPH依赖性氧化酶同时被激活的过程中,受刺激的中性粒细胞还会产生过氧化氢,通过这种方式,MPO-过氧化氢-卤化物系统发挥其强大的杀菌活性。最近对MPO的关注已远远超出了宿主对感染的固有防御领域,还包括全身性炎症性疾病、动脉粥样硬化和退行性神经疾病。利用MPO的cDNA序列搜索各种数据库,发现了在广泛不同物种中具有过氧化物活性的蛋白质之间以前未被怀疑的关系。此外,细胞和分子生物学分析工具的应用,使得能够确定MPO缺乏症背后的特定基因型,以及特定突变对MPO前体在生物合成途径中命运的影响。与此同时,此类研究在理解MPO生物合成和细胞内靶向的正常步骤方面取得了重大进展。

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1
Insights into myeloperoxidase biosynthesis from its inherited deficiency.从髓过氧化物酶遗传性缺乏症看其生物合成机制
J Mol Med (Berl). 1998 Sep;76(10):661-8. doi: 10.1007/s001090050265.
2
Quality control in the endoplasmic reticulum: lessons from hereditary myeloperoxidase deficiency.内质网中的质量控制:来自遗传性髓过氧化物酶缺乏症的教训。
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Effect of the R569W missense mutation on the biosynthesis of myeloperoxidase.R569W错义突变对髓过氧化物酶生物合成的影响。
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Clinical manifestation of myeloperoxidase deficiency.髓过氧化物酶缺乏症的临床表现。
J Mol Med (Berl). 1998 Sep;76(10):676-81. doi: 10.1007/s001090050267.
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Impact of missense mutations on biosynthesis of myeloperoxidase.错义突变对髓过氧化物酶生物合成的影响。
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Biosynthesis and processing of myeloperoxidase--a marker for myeloid cell differentiation.髓过氧化物酶的生物合成与加工——髓样细胞分化的标志物
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Molecular genetics of peroxidase deficiency.
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