Acute Hypoxia Stress-Induced Apoptosis in Gill of Japanese Flounder (Paralichthys olivaceus) by Modulating the Epas1/Bad Pathway

Abstract

The physiological responses and molecular mechanisms of apoptosis in Japanese flounder under hypoxic stress remain unclear. In the present study, we performed acute hypoxia stress on Japanese flounder (2.39 ± 0.84 mg/L) and detected gills responses in histomorphology and molecular mechanisms. The results showed that the volume of the interlamellar cell mass decreased and the gill lamellae prolonged, indicating the expansion of the respiratory surface area. Additionally, the fluorescence signal of apoptosis increased under hypoxic stress. In addition, the expression of two genes (EPAS1 and Bad) related to apoptosis increased about four-fold and two-fold, respectively, at 6 hours of hypoxia. Meanwhile, the result of the dual-luciferase reporter assay showed that EPAS1 is a transcription factor, which could regulate (p < 0.05) the expression of the Bad gene, and we identified the binding site of EPAS1 was the AATGGAAAC sequence located near −766. DNA methylation assay showed that hypoxia affected the methylation status of CpG islands of EPAS1 and Bad genes. All results indicated that hypoxia could activate the EPAS1/Bad signal pathway to induce gill apoptosis of Japanese flounder. Our study provides new light on understanding the molecular mechanism of hypoxia-induced apoptosis in Japanese flounder.

Uncovering the genetic diversity and adaptability of Butuo Black Sheep through whole-genome re-sequencing

“…It also stimulates the NF-κB signaling pathway and accelerates the loss of adipose tissue in hypoxia [ 49 ]. The BAD gene expression level increases 2-fold under hypoxia induction, and the methylation status of CpG islands is affected [ 50 ]. The BAD gene regulates cell apoptosis primarily by affecting the phosphorylation levels of Ser112, Ser136, and Ser155, participating in cell apoptosis regulations [ 51 ].…”