The transcriptomic responses of blunt snout bream (Megalobrama amblycephala) to acute hypoxia stress alone, and in combination with bortezomib

Abstract

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·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·L− 1 and 1.32 mg·L− 1) compared to the control group (LOEcrit, 0.73 mg·L− 1 and 0.85 mg·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.

Integration of physiological, miRNA‐mRNA interaction and functional analysis reveals the molecular mechanism underlying hypoxia stress tolerance in crucian carp (Carassius auratus)

“…Based on RNA‐seq data, we found that the DE mRNAs encoding the enzymes involved in the TCA cycle ( sdh , fh , and mdh ) were significantly downregulated and the DE mRNAs encoding the enzymes involved in glycolysis ( hk1 / hk2 , pfk , gapdh , pk , and ldh ) were clearly upregulated, and these genes were also differentially down‐ or upregulated at the remaining time points under hypoxia. Similar results have been reported for large yellow croaker 7,43 . These results suggested aerobic respiration was inhibited and a rapid adaptive activation of anaerobic ATP‐generating pathway under hypoxia stress.…”

“…In tilapia ( Oreochromis niloticus ), changes in glucose, lipid, and amino acid metabolism quickly occurred to hypoxia exposure 11 . Similar results were observed in rainbow trout ( Oncorhynchus mykiss ), 12 , 13 large yellow croaker ( Larimichthys crocea ), 14 and blunt snout bream ( Megalobrama amblycephala ) 7 . Besides, hypoxia stress also influenced immune responses of fish.…”

“…Epo is essential for erythropoiesis production 54 ; vegf is involved in angiogenesis process 55 ; and ho is a key player defense against cellular oxidative injury 56 . Analysis of the transcriptomic responses of blunt snout bream to hypoxia stress revealed that the mRNA levels of epo and vegf in the liver were significantly upregulated, but the expression of hif‐1α was only slightly increased relative to the control 7 . In addition, the expression of vegfa was markedly elevated in pufferfish ( Takifugu rubripes ) after hypoxia exposure, but not hif‐1α 57 .…”

Transcriptomic atlas for hypoxia and following re-oxygenation in Ancherythroculter nigrocauda heart and brain tissues: insights into gene expression, alternative splicing, and signaling pathways

“…Transcriptomic studies have been conducted about hypoxic stress in many fish species. In blunt snout bream ( Megalobrama amblycephala ) liver tissue, KEGG pathway enrichment analysis found that these differentially expressed genes (DEGs) were enriched in HIF-1, FOXO, MAPK, PI3K-Akt and AMPK signaling pathway ( Zhao et al, 2022 ). While in another Cyprinidae fish, silver carp ( Hypophthalmichthys molitrix ), KEGG enrichment analysis found a similar pattern that PI3K-Akt, FOXO and JAK-STAT were among most prominent pathway activated by hypoxia in heart tissue ( Li et al, 2021 ).…”

Transcriptome and 16S rRNA Analyses Reveal That Hypoxic Stress Affects the Antioxidant Capacity of Largemouth Bass (Micropterus salmoides), Resulting in Intestinal Tissue Damage and Structural Changes in Microflora

“…Using these techniques, researchers have unraveled a series of molecular changes in fish under hypoxic stress. It has been reported that in channel catfish (Ictalurus punctatus) [16] and blunt snout bream (Megalobrama amblycephala) [17], the pathways significantly enriched with differentially expressed genes (DEGs) under hypoxic stress are HIF-1, MAPK, and PI3K-Akt. The environmental stress caused by hypoxia reduces the oxygen transfer to the surrounding tissues.…”