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).