Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes
Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes
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DOI：
10.1016/j.bbrc.2006.04.008
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发表时间：
2006-06-09
影响因子：
3.1
通讯作者：
Kishi, Koichiro
中科院分区：
文献类型：
--
作者：
Iida, Reiko;Yasuda, Toshihiro;Kishi, Koichiro
M-LP（Mpv 17样蛋白）是一种最初在小鼠组织中鉴定的蛋白质，并且与Mpv 17蛋白（一种参与早发性肾小球硬化发展的过氧化物酶体膜蛋白）显示出高度序列同源性[R. Iida，T. Yasuda，E.坪田，H. Takatsuka，M. Masuyama，T. Matsuki，K. Kishi，M-LP，Mpv17-like protein，has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positive charged loop and upregulates expression of the manganese superoxide dismutase gene，J.Biol.Chem.278（2003）6301-6306]。在这里，我们报告的M-LP（M-LPH）基因的人类同源物的鉴定和表征。M-LPH基因由4个外显子组成，位于染色体16 p13上，长度超过14 kb。1，并且表达为分别包含四个和三个外显子的两个选择性剪接变体，其包括分别编码由196个（M-LPH 1）和147个（M-LPH 2）氨基酸组成的两种不同同种型的开放阅读框。这两种变体在人体组织中普遍表达，但在蛋白质水平上仅检测到M-LPH 1。用绿色荧光蛋白标记的M-LPH 1转染COS-7细胞，双色共聚焦分析表明，M-LPH 1定位于过氧化物酶体。为了阐明M-LPH 1的功能，我们检测了COS-7细胞中参与活性氧代谢的几种酶的mRNA水平，发现转染M-LPH 1下调血浆谷胱甘肽过氧化物酶和过氧化氢酶基因的表达。这些结果表明存在M-LP的人类同源物及其参与活性氧代谢。(c)2006年爱思唯尔公司All rights reserved.
M-LP (Mpv17-like protein) is a protein that was initially identified in mouse tissues and shows high sequence homology with Mpv17 protein, a peroxisomal membrane protein involved in the development of early-onset glomerulosclerosis [R. Iida, T. Yasuda, E. Tsubota, H. Takatsuka, M. Masuyama, T. Matsuki, K. Kishi, M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up-regulates expression of the manganese superoxide dismutase gene, J. Biol. Chem. 278 (2003) 6301-6306]. Here we report the identification and characterization of a human homolog of the M-LP (M-LPH) gene. The M-LPH gene is composed of four exons, extends over 14 kb on chromosome 16p 13. 1, and is expressed as two alternatively spliced variants comprising four and three exons, respectively, which include open-reading frames encoding two distinct isoforms composed of 196 (M-LPH I) and 147 (M-LPH2) amino acids, respectively. These two variants were expressed ubiquitously in human tissues, however only M-LPH1 was detected at the protein level. Dual-color confocal analysis of COS-7 cells transfected with a green fluorescent protein-tagged M-LPH1 demonstrated that M-LPH1 is localized in peroxisomes. In order to elucidate the function of M-LPH1, we examined the mRNA levels of several enzymes involved in the metabolism of reactive oxygen species in COS-7 cells and found that transfection with M-LPH1 down-regulates expression of the plasma glutathione peroxidase and catalase genes. These results show the existence of the human homolog of M-LP and its participation in reactive oxygen species metabolism. (c) 2006 Elsevier Inc. All rights reserved.