Cardiac Transcriptomics Reveals That MAPK Pathway Plays an Important Role in Hypoxia Tolerance in Bighead Carp (Hypophthalmichthys nobilis)

SIMPLE SUMMARY: Acute hypoxia treatment was performed in juvenile bighead carp (Hypophthalmicthys nobilis) by decreasing water O(2). The results showed that blood lactate and serum glucose increased significantly under hypoxia stress, and some differentially expressed genes were identified among hypoxia tolerant, hypoxia sensitive, and normoxia control groups. Differentially expressed genes between hypoxia tolerant and hypoxia sensitive groups were mainly involved in mitogen-activated protein kinase (MAPK) signaling, insulin signaling, apoptosis, tight junction, and adrenergic signaling in cardiomyocytes pathways, of which MAPK signaling pathway played a key role in cardiac tolerance to hypoxia in bighead carp. These results provide a basis for understanding the physiological and molecular mechanisms underlying hypoxia response in fish and a guide for future genetic breeding programs for hypoxia resistance in bighead carp. ABSTRACT: As aquatic animals, fishes often encounter various situations of low oxygen, and they have evolved the ability to respond to hypoxia stress. Studies of physiological and molecular responses to hypoxia stress are essential to clarify genetic mechanisms underlying hypoxia tolerance in fish. In this study, we performed acute hypoxia treatment in juvenile bighead carp (Hypophthalmicthys nobilis) by decreasing water O(2) from 6.5 mg/L to 0.5 mg/L in three hours. This hypoxia stress resulted in a significant increase in blood lactate and serum glucose. Comparisons of heart transcriptome among hypoxia tolerant (HT), hypoxia sensitive (HS), and normoxia control (NC) groups showed that 820, 273, and 301 differentially expressed genes (DEGs) were identified in HS vs. HT, NC vs. HS, and NC vs. HT (false discovery rate (FDR) < 0.01, Fold Change> 2), respectively. KEGG pathway enrichment showed that DEGs between HS and HT groups were mainly involved in mitogen-activated protein kinase (MAPK) signaling, insulin signaling, apoptosis, tight junction and adrenergic signaling in cardiomyocytes pathways, and DEGs in MAPK signaling pathway played a key role in cardiac tolerance to hypoxia. Combined with the results of our previous cDNA-amplified fragment length polymorphism (cDNA-AFLP) analysis of hypoxia stress in this species, such genes as stbp2, ttn, mapk, kcnh, and tnfrsf were identified in both studies, representing the significance of these DEGs in hypoxia tolerance in bighead carp. These results provide insights into the understanding of genetic modulations for fish heart coping with hypoxia stress and generate basic resources for future breeding studies of hypoxia resistance in bighead carp.