Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene
Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene
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DOI：
10.1016/j.gene.2004.04.002
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发表时间：
2004-07-21
期刊：
影响因子：
3.5
通讯作者：
Noguchi, M
中科院分区：
文献类型：
--
作者：
Hayashi, S;Omata, Y;Noguchi, M
血红素加氧酶（HO）是一种负责血红素生理降解产生铁、CO和胆绿素的酶。释放的铁被回收，并代表血红素体内平衡中这种金属的主要来源。一个假定的作用，作为信使的信号通路中建议CO。胆绿素，连同胆红素，可能作为一种抗氧化剂。到目前为止，已经描述了HO的三种同种型，HO-1、HO-2和HO-3。虽然HO-1和HO-2已被广泛研究，但HO-3 [McCoubrey W.M. Jr，Huang，T.J.，缅因州，医学博士EUR. J.Biochem.247（1997）725-732]仍然是一种难以捉摸且知之甚少的同种型。本研究采用基因组PCR技术对大鼠HO-3基因进行了结构分析。然而，我们未能分离出报道的HO-3基因，而是发现了两个HO-3相关基因，暂命名为HO-3a和HO-3b，其序列彼此略有不同。这两个基因都没有任何内含子，并且仅由HO-2基因的外显子2至5组成，尽管它们的序列与HO-2的序列不完全相同。由于移码，在这些基因的编码区域内引入终止密码子。其5 ′上游区核苷酸序列与长散布核元件3基本一致。RT-PCR未检测到HO-3相关mRNA，Western blot检测未检测到HO-3相关蛋白。本研究结果提示，大鼠体内不存在功能性HO-3基因，HO-3a和HO-3b基因是由HO-2转录本衍生的加工假基因。(C)2004 Elsevier B. V.保留所有权利。
Heme oxygenase (HO) is an enzyme responsible for the physiological degradation of heme to produce iron, CO and biliverdin. The released iron is recycled and represents the major source of this metal in heme homeostasis. A putative role as messenger in a signaling pathway is suggested for CO. Biliverdin, together with bilirubin, may function as an antioxidant. Thus far, three isoforms of HO, HO-1, HO-2 and HO-3 have been described. While HO-1 and HO-2 have been extensively investigated, HO-3 [McCoubrey W.M. Jr, Huang, T.J., Maines, M.D. Eur. J. Biochem. 247 (1997) 725-732] is still an elusive and poorly understood isoform. In this study, we examined the structure of the rat HO-3 gene with genomic PCR. However, we failed to isolate the reported HO-3 gene but, instead, found two HO-3-related genes, tentatively named HO-3a and HO-3b, whose sequences differed slightly from each other. Neither gene had any introns and consisted only of exon 2 through 5 of the HO-2 gene, though their sequences were not completely identical with that of HO-2. A stop codon was introduced within the coding regions of these genes due to frame-shift. The nucleotide sequence of their 5'-upstream region largely agreed with long interspersed nuclear element 3. No HO-3-related mRNAs were amplified by RT-PCR, and no HO-3-related proteins were detected in tissues by Western blot analysis. Our results suggested that there are no functional HO-3 genes in rat and that the HO-3a and HO-3b genes are processed pseudogenes derived from HO-2 transcripts. (C) 2004 Elsevier B.V. All rights reserved.