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

Ying Zhou,Junru Wang,Xiaomu Yu,Weiwei Luo,Jingou Tong,Yizhao Feng

doi:10.3390/ani10091483

Abstract

Simple SummaryAcute hypoxia treatment was performed in juvenile bighead carp (Hypophthalmicthys nobilis) by decreasing water O2. 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.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 O2 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.

Highlights

Aquatic animals such as fish are frequently exposed to hypoxic environments owing to low atmospheric pressure and eutrophication in water [1,2]
Glucose and lactic acid were found to be significantly increased under lower oxygen concentration, but there was no difference between hypoxia sensitive (HS) and hypoxia tolerant (HT) groups (Figure 1)
Hemoglobin (Hb) was expected to increase as oxygen concentration decreased; there were no significant treatment effects seen about Hb between control and hypoxia stress groups (Figure 1)

Summary

Introduction

Aquatic animals such as fish are frequently exposed to hypoxic environments owing to low atmospheric pressure and eutrophication in water [1,2]. Hypoxia stress limits the transport of dissolved oxygen (DO) across the gill membrane and the level of cellular metabolic activity, which inhibits vital activities of the whole organism in turn, including feeding and growth [4]. Hypoxic death is relevant to catastrophic loss of substrate, failure of vital adenosine triphosphate (ATP) consuming processes, accumulation of toxic levels of waste products (protons/lactate), and cellular necrosis [5]. Many responses for fish to adopt different mechanisms to tolerate hypoxia are behavioral, including surface breathing, reduced activity, or increased ventilation rate [6]. Fish exhibit adaptive responses to hypoxia, including discontinuation of processes requiring substantial energy output, such as cell growth/proliferation, protein synthesis, and locomotion [7,8]. Unearthing the molecular mechanisms of hypoxia adaptation and tolerance in fishes will help us to understand evolution of the hypoxia-related signaling pathway and guide us in the breeding of hypoxia-tolerant fish strains [10]

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