Shirota S, Yoshida T, Sakai M, Kim J I, Sugiura H, Oishi T, Nitta K, Tsuchiya K
Department of Medicine IV, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Biochem Biophys Res Commun. 2006 Sep 22;348(2):501-6. doi: 10.1016/j.bbrc.2006.07.111. Epub 2006 Jul 28.
Large mafs are transcriptional factors and members of the basic leucine zipper (b-Zip) superfamily. Since we previously identified expression of c-maf in mouse kidney, we presently investigated the mRNA expression profile in the kidney of c-maf gene knockout mice by using DNA microarray, and plasma glutathione peroxidase-3 (GPx3) was predominantly downregulated. We focused on the relation between the expression level of c-maf and GPx3 in vivo and in vitro. Since GPx3 is an antioxidant enzyme, oxidative stress was induced by exposing a culture cell derived from mouse renal tubules (mIMCD3) to hydrogen peroxide. Real-time PCR demonstrated that mRNA expression of both c-maf and GPx3 increased in parallel during exposure to oxidative stress in a time- and dose-dependent manner. Then, the mIMCD3 cells were transfected with c-maf-cDNA containing plasmid, which resulted in an increase in mRNA and protein expression of GPx3 compared with the control cells. Thus, c-maf may be transcriptional regulator of GPx3 expression and modulate the antioxidative pathway in the kidney.
大型maf蛋白是转录因子,属于碱性亮氨酸拉链(b-Zip)超家族成员。由于我们之前已鉴定出c-maf在小鼠肾脏中的表达,我们目前通过DNA微阵列研究了c-maf基因敲除小鼠肾脏中的mRNA表达谱,发现血浆谷胱甘肽过氧化物酶-3(GPx3)主要下调。我们着重研究了体内和体外c-maf表达水平与GPx3之间的关系。由于GPx3是一种抗氧化酶,通过将源自小鼠肾小管的培养细胞(mIMCD3)暴露于过氧化氢来诱导氧化应激。实时PCR表明,在暴露于氧化应激期间,c-maf和GPx3的mRNA表达以时间和剂量依赖性方式平行增加。然后,用含c-maf-cDNA的质粒转染mIMCD3细胞,与对照细胞相比,这导致GPx3的mRNA和蛋白质表达增加。因此,c-maf可能是GPx3表达的转录调节因子,并调节肾脏中的抗氧化途径。