Xenopus gpx3 Mediates Posterior Development by Regulating Cell Death during Embryogenesis

• Published in: Antioxidants 2020-12, Vol.9 (12), p.1265
• Main Authors: Lee, Hongchan, Ismail, Tayaba, Kim, Youni, Chae, Shinhyeok, Ryu, Hong-Yeoul, Lee, Dong-Seok, Kwon, Taeg Kyu, Park, Tae Joo, Kwon, Taejoon, Lee, Hyun-Shik
• Format: Article
• Language: English
• Subjects: Antioxidants; Antisense oligonucleotides; Apoptosis; Bone morphogenetic proteins; Cell death; Cell proliferation; Coronary artery disease; Deoxyribonucleic acid; Developmental stages; DNA; DNA methylation; DNA nucleotidylexotransferase; Eggs; Embryogenesis; Embryos; Fluorescent indicators; Gene expression; Genes; Glutathione peroxidase; gpx3; Heart diseases; Histones; Homeostasis; Hybridization; Hydrogen peroxide; Liver diseases; Localization; Mammals; Metastases; Oligonucleotides; Polymerase chain reaction; posterior development; Reactive oxygen species; Reverse transcription; Ribonucleic acid; RNA; RNA polymerase; Selenoproteins; Software; tailbud; Tails; Testes
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox9121265

Glutathione peroxidase 3 (GPx3) belongs to the glutathione peroxidase family of selenoproteins and is a key antioxidant enzyme in multicellular organisms against oxidative damage. Downregulation of GPx3 affects tumor progression and metastasis and is associated with liver and heart disease. However, the physiological significance of GPx3 in vertebrate embryonic development remains poorly understood. The current study aimed to investigate the functional roles of during embryogenesis. To this end, we determined 's spatiotemporal expression using as a model organism. Using reverse transcription polymerase chain reaction (RT-PCR), we demonstrated the zygotic nature of this gene. Interestingly, the expression of enhanced during the tailbud stage of development, and whole mount in situ hybridization (WISH) analysis revealed localization in prospective tail region of developing embryo. knockdown using antisense morpholino oligonucleotides (MOs) resulted in short post-anal tails, and these malformed tails were significantly rescued by glutathione peroxidase mimic ebselen. The gene expression analysis indicated that knockdown significantly altered the expression of genes associated with Wnt, Notch, and bone morphogenetic protein (BMP) signaling pathways involved in tailbud development. Moreover, RNA sequencing identified that plays a role in regulation of cell death in the developing embryo. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and phospho-histone 3 (PH3) staining confirmed the association of knockdown with increased cell death and decreased cell proliferation in tail region of developing embryos, establishing the involvement of in tailbud development by regulating the cell death. Furthermore, these findings are inter-related with increased reactive oxygen species (ROS) levels in knockdown embryos, as measured by using a redox-sensitive fluorescent probe HyPer. Taken together, our results suggest that plays a critical role in posterior embryonic development by regulating cell death and proliferation during vertebrate embryogenesis.