College of Fisheries, Guangdong Ocean University, Zhanjiang 524088, China.
Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China.
Int J Mol Sci. 2024 Jan 15;25(2):1054. doi: 10.3390/ijms25021054.
is an economically important mariculture fish, and hypoxia has become a critical threat to this hypoxia-sensitive species. However, the molecular adaptation mechanism of liver to hypoxia remains unclear. In this study, we investigated the effects of acute hypoxic stress (1.5 ± 0.1 mg·L for 6 h) and re-oxygenation (5.8 ± 0.3 mg·L for 12 h) in liver at both the transcriptomic and metabolic levels to elucidate hypoxia adaptation mechanism. Integrated transcriptomics and metabolomics analyses identified 36 genes and seven metabolites as key molecules that were highly related to signal transduction, cell growth and death, carbohydrate metabolism, amino acid metabolism, and lipid metabolism, and all played key roles in hypoxia adaptation. Of these, the hub genes and were pivotal hypoxia adaptation biomarkers for regulating cell growth and death. During hypoxia, up-regulation of and genes induced cell cycle arrest. Enhancing intrinsic and extrinsic pathways in combination with glutathione metabolism triggered apoptosis; meanwhile, anti-apoptosis mechanism was activated after hypoxia. Expression of genes related to glycolysis, gluconeogenesis, amino acid metabolism, fat mobilization, and fatty acid biosynthesis were up-regulated after acute hypoxic stress, promoting energy supply. After re-oxygenation for 12 h, continuous apoptosis favored cellular function and tissue repair. Shifting from anaerobic metabolism (glycolysis) during hypoxia to aerobic metabolism (fatty acid β-oxidation and TCA cycle) after re-oxygenation was an important energy metabolism adaptation mechanism. Hypoxia 6 h was a critical period for metabolism alteration and cellular homeostasis, and re-oxygenation intervention should be implemented in a timely way. This study thoroughly examined the molecular response mechanism of under acute hypoxic stress, which contributes to the molecular breeding of hypoxia-tolerant cultivars.
是一种具有重要经济价值的海水养殖鱼类，而缺氧已成为该鱼类面临的关键威胁。然而，其肝脏对缺氧的分子适应机制尚不清楚。在这项研究中，我们在转录组和代谢组水平上研究了急性缺氧应激（1.5±0.1 mg·L，持续 6 小时）和再复氧（5.8±0.3 mg·L，持续 12 小时）对肝脏的影响，以阐明缺氧适应机制。整合转录组学和代谢组学分析确定了 36 个基因和 7 种代谢物作为与信号转导、细胞生长和死亡、碳水化合物代谢、氨基酸代谢和脂质代谢高度相关的关键分子，它们在缺氧适应中都发挥了关键作用。其中，基因和是调节细胞生长和死亡的关键缺氧适应生物标志物。在缺氧条件下，基因和的上调诱导细胞周期停滞。增强内在和外在途径以及谷胱甘肽代谢会引发细胞凋亡；同时，在缺氧后激活了抗凋亡机制。在急性缺氧应激后，与糖酵解、糖异生、氨基酸代谢、脂肪动员和脂肪酸生物合成相关的基因表达上调，从而促进能量供应。在复氧 12 小时后，持续的细胞凋亡有利于细胞功能和组织修复。从缺氧时的无氧代谢（糖酵解）到复氧后的有氧代谢（脂肪酸β-氧化和 TCA 循环）的转变是一种重要的能量代谢适应机制。缺氧 6 小时是代谢改变和细胞内稳态的关键时期，应及时进行复氧干预。本研究全面研究了在急性缺氧应激下的分子响应机制，为耐缺氧品种的分子选育提供了参考。
