Egawa K, Yoshiwara M, Shibanuma M, Nose K
Department of Microbiology, Showa University, School of Pharmaceutical Sciences, Tokyo, Japan.
FEBS Lett. 1995 Sep 18;372(1):74-7. doi: 10.1016/0014-5793(95)00957-b.
Hydrogen peroxide appears to mediate growth factor actions, and it inhibits DNA synthesis in normal mouse osteoblastic cells (MC3T3-E1) at non-toxic doses. However the sensitivity of cells to H2O2 is greatly decreased in their ras-transformants. To understand the molecular basis of this sensitivity to H2O2, we attempted to identify H2O2-inducible cDNA clones from MC3T3 cells by differential screening of cDNA libraries, and one of such genes, named HIC-53, was isolated. The level of HIC-53 mRNA was moderately increased by H2O2 as well as by calcium ionophore or dexamethasone, but was not increased by the addition of serum, tumor promoting phorbol ester, or epidermal growth factor. Among mouse organs, HIC-53 mRNA levels were higher in the kidney and lung, but were almost undetectable in the brain, heart, bone, muscle or spleen. In MC3T3 cells transformed with v-Ki-ras, the HIC-53 mRNA level was markedly decreased, and effect of H2O2 was abolished. Although the biological function of HIC-53 is unknown at present, the predicted amino acid sequence exhibited some similarity with bovine cardiac Na+/Ca+ exchanger. The nucleotide sequence of HIC-53 cDNA showed no significant similarity with other known gene sequences.
过氧化氢似乎介导生长因子的作用，并且它在无毒剂量下抑制正常小鼠成骨细胞（MC3T3-E1）中的DNA合成。然而，在其ras转化细胞中，细胞对H2O2的敏感性大大降低。为了理解这种对H2O2敏感性的分子基础，我们试图通过对cDNA文库进行差异筛选，从MC3T3细胞中鉴定出H2O2诱导的cDNA克隆，并分离出其中一个名为HIC-53的基因。H2O2、钙离子载体或地塞米松可适度提高HIC-53 mRNA的水平，但添加血清、促肿瘤佛波酯或表皮生长因子则不会使其升高。在小鼠器官中，HIC-53 mRNA水平在肾脏和肺中较高，但在脑、心脏、骨骼、肌肉或脾脏中几乎检测不到。在用v-Ki-ras转化的MC3T3细胞中，HIC-53 mRNA水平显著降低，并且H2O2的作用消失。尽管目前HIC-53的生物学功能尚不清楚，但预测的氨基酸序列与牛心脏Na+/Ca+交换体有一些相似性。HIC-53 cDNA的核苷酸序列与其他已知基因序列没有显著相似性。
