Genetics and Breeding Center for Blunt Snout Bream, Ministry of Agriculture, Shanghai, 201306, China.
Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai, 201306, China.
BMC Genomics. 2022 Feb 25;23(1):162. doi: 10.1186/s12864-022-08399-7.
Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia. A new blunt snout bream strain, "Pujiang No.2", was developed to overcome this shortcoming. As a proteasome inhibitor, bortezomib (PS-341) has been shown to affect the adaptation of cells to a hypoxic environment. In the present study, bortezomib was used to explore the hypoxia adaptation mechanism of "Pujiang No.2". We examined how acute hypoxia alone (hypoxia-treated, HN: 1.0 mg·L), and in combination with bortezomib (hypoxia-bortezomib-treated, HB: Use 1 mg bortezomib for 1 kg fish), impacted the hepatic ultrastructure and transcriptome expression compared to control fish (normoxia-treated, NN).
Hypoxia tolerance was significantly decreased in the bortezomib-treated group (LOE, loss of equilibrium, 1.11 mg·L and 1.32 mg·L) compared to the control group (LOE, 0.73 mg·L and 0.85 mg·L). The HB group had more severe liver injury than the HN group. Specifically, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the HB group (52.16 U/gprot, 32 U/gprot) were significantly (p < 0.01) higher than those in the HN group (32.85 U/gprot, 21. 68 U/gprot). In addition, more severe liver damage such as vacuoles, nuclear atrophy, and nuclear lysis were observed in the HB group. RNA-seq was performed on livers from the HN, HB and NN groups. KEGG pathway analysis disclosed that many DEGs (differently expressed genes) were enriched in the HIF-1, FOXO, MAPK, PI3K-Akt and AMPK signaling pathway and their downstream.
We explored the adaptation mechanism of "Pujiang No.2" to hypoxia stress by using bortezomib, and combined with transcriptome analysis, accurately captured the genes related to hypoxia tolerance advantage.
钝吻鲂对低氧敏感。为克服这一缺点，培育出了一个新的钝吻鲂品系“浦江 2 号”。蛋白酶体抑制剂硼替佐米（PS-341）已被证明会影响细胞对低氧环境的适应。本研究用硼替佐米来探索“浦江 2 号”的低氧适应机制。我们检测了单纯急性低氧（低氧处理，HN：1.0mg·L-1）以及与硼替佐米联合处理（低氧-硼替佐米处理，HB：每公斤鱼使用 1mg 硼替佐米）与对照组（常氧处理，NN）相比，对肝脏超微结构和转录组表达的影响。
与对照组（LOE，失衡，0.73mg·L-1 和 0.85mg·L-1）相比，硼替佐米处理组（LOE，1.11mg·L-1 和 1.32mg·L-1）的耐低氧能力显著降低。HB 组的肝损伤比 HN 组更严重。具体而言，HB 组的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性（52.16U/gprot，32U/gprot）显著（p<0.01）高于 HN 组（32.85U/gprot，21.68U/gprot）。此外，HB 组还观察到更严重的肝损伤，如空泡、核萎缩和核溶解。对 HN、HB 和 NN 组的肝脏进行了 RNA-seq 分析。KEGG 通路分析揭示，许多差异表达基因（DEGs）在 HIF-1、FOXO、MAPK、PI3K-Akt 和 AMPK 信号通路及其下游通路中富集。
我们用硼替佐米探索了“浦江 2 号”对低氧胁迫的适应机制，并结合转录组分析，准确捕获了与低氧耐受力优势相关的基因。
