Meeting Abstract

P2.170  Sunday, Jan. 5 15:30  Hypoxia-induced global DNA methylation and IGF regulation in a marine teleost, red snapper RAHMAN, M.S.*; THOMAS, P.; University of Texas at Austin; University of Texas at Austin rahman@utexas.edu

Epigenetic modifications such as DNA methylation and histone acetylation impact developmental processes in vertebrates. However, little is known about the epigenetic modifications occurring in aquatic vertebrates during exposure to environmental stress. In this study, we investigated the changes in global DNA methylation and regulation of the related enzyme, DNA methyltransferase (DNMT) as well as the expression of insulin-like growth factor-I (IGF-I) in hepatic tissues after chronic exposure of red snapper to hypoxia (dissolved oxygen 1.7 mg/L for 4 weeks). Colorimetric in situ TUNEL assay and immunoreactive (IR) staining were conducted to evaluate DNA fragmentation and global DNA methylation, respectively. Plasma IGF-I levels were measured by enzyme immunoassay to determine whether changes in IGF-I regulation are associated with the changes in global DNA methylation during hypoxia exposure. Chronic hypoxia exposure caused marked increases in the immunoreactive expression of ssDNA, dsDNA, and 8-hydroxy-2-deoxy guanosine, a key marker of oxidative DNA damage, in hepatic tissues. Massive DNA damage detected by TUNEL signals was also observed in hepatocytes after hypoxia exposure. The IR intensities of DNMT, 5-methylcytosine (5mC, a methylated form of DNA base cytosine), and histone H3K4 trimethyl (H3K4me3, a histone protein involved in the structure of chromatin) were markedly increased in hepatic tissues after hypoxia exposure. In addition, hypoxia exposure caused a marked decline in plasma IGF-I levels to 25% of original levels. Collectively these results suggest that hypoxia leads to induction of DNA methylation through the related enzyme, DNMT, which might be involved in the regulation hepatic IGF-I expression in aquatic vertebrates.