Journal
BMC GENOMICS
Volume 23, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12864-022-08399-7
Keywords
Hypoxia; Megalobrama amblycephala; Liver; Bortezomib; Transcriptome
Funding
- National Key Research and Development Blue Granary Technology Innovation key project [2020YFD0900400]
- Capacity Building Plan of Shanghai Local Colleges and Universities [18050501900]
- China Postdoctoral Science Foundation [2019 M651473]
- (Guo-Dong Zheng)
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This study used bortezomib to explore the adaptation mechanism of Pujiang No.2 to hypoxia stress and accurately identified the genes related to hypoxia tolerance advantage through transcriptome analysis.
Background 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 center dot L- 1), 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). Results Hypoxia tolerance was significantly decreased in the bortezomib-treated group (LOEcrit, loss of equilibrium, 1.11 mg center dot L- 1 and 1.32 mg center dot L- 1) compared to the control group (LOEcrit, 0.73 mg center dot L- 1 and 0.85 mg center dot L- 1). 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. Conclusion 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.
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