Biochemistry, Biophysics, and Structural Biology Commons^™

Modulating Glutathione Thiol Status Alters Pancreatic Β-Cell Morphogenesis In The Developing Zebrafish (Danio Rerio) Embryo, Archit Rastogi, Emily G. Severance, Haydee M. Jacobs, Sarah M. Conlin, Sadia T. Islam, Alicia R. Timme-Laragy

Environmental Health Sciences Faculty Publication Series

Emerging evidence suggests that redox-active chemicals perturb pancreatic islet development. To better understand potential mechanisms for this, we used zebrafish (Danio rerio) embryos to investigate roles of glutathione (GSH; predominant cellular redox buffer) and the transcription factor Nrf2a (Nfe2l2a; zebrafish Nrf2 coortholog) in islet morphogenesis. We delineated critical windows of susceptibility to redox disruption of beta-cell morphogenesis, interrogating embryos at 24, 48 and 72 h post fertilization (hpf) and visualized Nrf2a expression in the pancreas using whole-mount immunohistochemistry at 96 hpf. Chemical GSH modulation at 48 hpf induced significant islet morphology changes at 96 hpf. Pro-oxidant exposures to tert-butylhydroperoxide (77.6 …