Zhou Yong, Ma Chunqi, Karmouch Jennifer, Katbi Hadia Arabi, Liu X Johné
Ottawa Health Research Institute, Ottawa Hospital, 725 Parkdale Avenue, Ottawa K1Y 4E9, Canada.
Mol Cell Biol. 2009 Apr;29(7):1786-95. doi: 10.1128/MCB.01815-08. Epub 2009 Jan 21.
Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is a nonredundant and essential gene in all eukaryotes. During the mitotic cell cycle, ODC exhibits two activity peaks: one at the G(1)/S transition and one during the G(2)/M transition. The physiological role of this cell cycle-dependent ODC activity dynamic is not clear. Previous studies have reported a significant elevation of ODC activity during Xenopus oocyte maturation, which resembles mitotic G(2)/M transition. In order to study the roles of ODC activity in the oocytes, we utilized antisense morpholino (xODC mo) oligonucleotides to inhibit ODC translation. We report here that xODC mo abolished ODC activity increase during oocyte maturation. xODC mo-injected oocytes underwent germinal vesicle breakdown, emitted the first polar body, and reached metaphase II, thus completing nuclear maturation. However, the metaphase II oocytes exhibited high levels of reactive oxygen species and became apoptotic. When transferred to host frogs and subsequently ovulated, these eggs were fertilized but exhibited embryo fragmentation. Translation of ODC is therefore integral to cytoplasmic maturation, protecting metaphase II oocytes from reactive oxygen species-induced apoptosis.
鸟氨酸脱羧酶(ODC)是多胺生物合成中的限速酶,在所有真核生物中都是一个不可替代的必需基因。在有丝分裂细胞周期中,ODC表现出两个活性峰值:一个在G(1)/S期转换时,另一个在G(2)/M期转换时。这种细胞周期依赖性ODC活性动态变化的生理作用尚不清楚。先前的研究报道,非洲爪蟾卵母细胞成熟过程中ODC活性显著升高,这类似于有丝分裂G(2)/M期转换。为了研究ODC活性在卵母细胞中的作用,我们利用反义吗啉代(xODC mo)寡核苷酸抑制ODC翻译。我们在此报告,xODC mo消除了卵母细胞成熟过程中ODC活性的增加。注射了xODC mo的卵母细胞经历了生发泡破裂,排出了第一极体,并达到了中期II,从而完成了核成熟。然而,中期II卵母细胞表现出高水平的活性氧并发生凋亡。当转移到宿主青蛙体内并随后排卵时,这些卵受精但出现胚胎碎片化。因此,ODC的翻译对于细胞质成熟是不可或缺的,可保护中期II卵母细胞免受活性氧诱导的凋亡。