Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
Comp Biochem Physiol A Mol Integr Physiol. 2019 Apr;230:81-90. doi: 10.1016/j.cbpa.2019.01.005. Epub 2019 Jan 16.
Lake whitefish (Coregonus clupeaformis) embryos and larvae were exposed to hypoxia at different developmental ages to determine when the cellular response to hypoxia could be initiated. mRNA levels of hypoxia-inducible factor 1α (hif-1α), hsp70, and several HIF-1 target genes were quantified in embryos at 21, 38, 63, 83- and 103-days post fertilisation (dpf) and in larvae at 1, 2, 3- and 4-weeks post hatch (wph) following a 6-hour hypoxia exposure. hsp70 mRNA levels were increased in response to hypoxia at all embryonic ages. By comparison, the first observed change in hif-1α mRNA in response to hypoxia was at 38 dpf, where it was down-regulated from high basal levels, with this response persisting through to 83 dpf. Interestingly, this decrease in hif-1α mRNA coincided with increases in the mRNA levels of the HIF-1 target genes: vegfa (vascular endothelial growth factor A), igfbp1 (insulin-like growth factor binding protein 1), ldha (lactate dehydrogenase a), gapdh (glyceraldehyde-3-phosphate dehydrogenase) and epo (erythropoietin) at select ages. Collectively, this suggests a possible HIF-1-mediated response to hypoxia despite a decrease in hif-1α mRNA. Coinciding with a decrease in basal levels, increases in hif-1α were measured in response to hypoxia at 103 dpf and in larval fish at 1, 2 and 3 wph but there were no consistent increases in HIF-1 target genes at these ages. Overall, our findings indicate that lake whitefish can mount a response to hypoxia early in embryogenesis which may mitigate some of the damaging effects of exposure to low oxygen levels at these critical life history stages.
湖白鲑（Coregonus clupeaformis）胚胎和幼鱼在不同的发育时期暴露于缺氧环境中，以确定何时可以启动细胞对缺氧的反应。在受精后 21、38、63、83-和 103 天的胚胎以及孵化后 1、2、3-和 4 周的幼鱼中，定量测定了缺氧诱导因子 1α（hif-1α）、hsp70 和几种 HIF-1 靶基因的 mRNA 水平，在经历 6 小时缺氧暴露后。hsp70 mRNA 水平在所有胚胎龄段均因缺氧而增加。相比之下，hif-1α mRNA 对缺氧的首次观察到的变化发生在 38 天，其从高基础水平下调，这种反应持续到 83 天。有趣的是，hif-1α mRNA 的减少与 HIF-1 靶基因的 mRNA 水平的增加相吻合：vegfa（血管内皮生长因子 A）、igfbp1（胰岛素样生长因子结合蛋白 1）、ldha（乳酸脱氢酶 a）、gapdh（甘油醛-3-磷酸脱氢酶）和 epo（促红细胞生成素）在特定年龄。总的来说，这表明尽管 hif-1α mRNA 减少，但存在可能的 HIF-1 介导的对缺氧的反应。与基础水平的降低相吻合，在 103 天的胚胎和 1、2 和 3 周龄的幼鱼中测量到 hif-1α 对缺氧的反应增加，但在这些年龄阶段，HIF-1 靶基因没有一致的增加。总的来说，我们的研究结果表明，湖白鲑在胚胎发生早期就可以对缺氧做出反应，这可以减轻在这些关键生命史阶段暴露于低氧水平的一些破坏性影响。
