Duttaroy A, Parkes T, Emtage P, Kirby K, Boulianne G L, Wang X, Hilliker A J, Phillips J P
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
DNA Cell Biol. 1997 Apr;16(4):391-9. doi: 10.1089/dna.1997.16.391.
The gene encoding manganese superoxide dismutase (MnSOD) from Drosophila melanogaster has been isolated and its expression has been studied. In contrast to several mammalian MnSOD genes, the Drosophila gene contains a single intron and is transcribed into a single 0.8-kb transcript. Whole-mount in situ hybridization reveals extensive transcript accumulation in ovarian nurse cells and a heavy maternal contribution to the early embryo. Larval imaginal discs are enriched with MnSOD transcripts relative to other larval tissues, further suggesting a possible relationship between high MnSOD expression and mitotic activity. The 5'-upstream region contains several well-known regulatory elements including metal response, antioxidant response, and xenobiotic response elements (MRE, ARE, and XRE, respectively), sites for activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), adenosine 3',5'-cyclic monophosphate regulator binding element factor (CREB), as well as classic TATA and CAAT boxes. That MnSOD expression in Drosophila is regulated in part by the transcription factor AP-1 via the MAP kinase signal transduction pathway is suggested by experiments which show that a hypomorphic mutation of the MAP kinase-encoding rolled gene substantially reduces levels of MnSOD transcripts and correlates with reduced resistance to oxidative stress in rolled mutants.
果蝇中编码锰超氧化物歧化酶(MnSOD)的基因已被分离出来,并对其表达进行了研究。与几种哺乳动物的MnSOD基因不同,果蝇基因只含有一个内含子,转录成一个0.8 kb的转录本。整体原位杂交显示,卵巢滋养细胞中有大量转录本积累,且母体对早期胚胎有大量贡献。相对于其他幼虫组织,幼虫的成虫盘富含MnSOD转录本,这进一步表明高MnSOD表达与有丝分裂活性之间可能存在关联。5'上游区域包含几个众所周知的调控元件,包括金属反应元件、抗氧化反应元件和外源性物质反应元件(分别为MRE、ARE和XRE)、激活蛋白-1(AP-1)、核因子-κB(NF-κB)、腺苷3',5'-环磷酸调节结合元件因子(CREB)的结合位点,以及经典的TATA盒和CAAT盒。实验表明,编码MAP激酶的rolled基因的亚等位基因突变会大幅降低MnSOD转录本水平,并与rolled突变体对氧化应激的抗性降低相关,这表明果蝇中MnSOD的表达部分受转录因子AP-1通过MAP激酶信号转导途径调控。