4.3 Muscle function
Our previous research found that in P. vachelli liver and brain tissues, the oxidative stress indices and antioxidant enzymatic activities were activated to varying degrees induced by hypoxia (Zhang et al. 2016a). Similarly, we detected upregulated Mn-SOD and GSTM/T3 mRNAs in P. vachellimuscles (Table 1 ). These might promote the inflammasome activation and trigger the ROS-induced apoptotic pathway (Giraud-Billoud et al. 2019).
(1) Inflammatory response
Several of the KEGG pathways, enriched by transcriptomes with a large proportion of upregulated genes were associated with human immune (e.g., B cell receptor signaling pathway and Type II diabetes mellitus) and inflammation (e.g., NAFLD, NOD-like receptor and Fc epsilon RI signaling pathway). Of note, the NOD-like receptor signaling pathway with 27 upregulated genes may offer insight into the molecular adaptations involved in hypoxia response (Fig. 2A ). NLRs (NLRC3/P3/P12, up-regulated) sense the cytosolic presence of DAMP, mainly from mitochondria (e.g., ROS and mtDNA). Then NLRs drove the activation of NF-kappa-B (IFNGR1/IKBKG/NFKBIB/CHUK, up-regulated) and MAPK (MAPKAPK5/Map4k2/Map2k4, up-regulated), cytokine production and apoptosis (Chen et al. 2014; Ko et al. 2017). Alternatively, a different set of NLRs induced caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. The activated of caspase-1 regulates maturation of the pro-inflammatory cytokines IL-1βand drives mitochondrial dysfunction and apoptosis (Liu et al. 2018; Yi et al. 2015)(Table 1 ).
(2) Apoptosis
Studies have shown that the apoptosis of fish brain and cardiac cells in the hypoxic state is one of the main causes of ”pond turnover” (Xiao 2015). Researchers have detected caspase-3/9 or apoptotic index, and found that hypoxia stress can induce apoptosis of fish neural, liver or cardiac cells, e.g., Acipenser shrenckii(Lu et al. 2005),Gymnocephalus cernua , Platichthys flesus(Tiedke et al. 2014) and M. amblycephala (Sun et al. 2017). We first found that there was a significant cell cycle arrest (CDK10/12/13/CCNI/YWHAZ, MCM4/7 down-regulated, CCNG2/DIDO1/MDC1/CDKN1B/GADD45A up-regulated) in P. vachellimuscles under hypoxia (Table 1 ), which may be due to the blocked energy metabolism and inflammatory response (Skovira et al. 2016). C-fos and HMGB1/3 were often the marker of cell apoptosis, and plays a significant role in hypoxia or ischemia induced apoptosis, which were significantly upregulated in P. vachelli muscle (Fig.6 ) (Brunelle& Chandel 2002). “Apoptosis” was also significantly enriched in KEGG pathway enrichment analysis of miRNA-mRNA pairs( Fig. 3A).