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Author Notes:

Address correspondence to: Alicia Timme-Laragy, Department of Public Health; School of Public Health and Health Sciences, University of Massachusetts Amherst, Goessmann 149C, 686 North Pleasant St., Amherst, MA 01003-9298. Phone: 1-413-545-7423, aliciat@schoolph.umass.edu

The authors kindly acknowledge the excellent fish care provided by Ms. Gale Clark, microarray data analysis provided by Dr. Andrew MacArthur, and technical assistance provided by Ms. Diana Franks.

We would also like to acknowledge assistance with GST identification by Dr. Juliano Zanette and Mr. Mauricio Sopezki.

We also thank the Center for Cystic Fibrosis Research of the Emory+Children’s Health Care of Atlanta.

The sponsors had no involvement in performing or in the decision to publish this study.

The U.S. Government is authorized to produce and distribute reprints for governmental purposes notwithstanding any copyright notation that may appear hereon.

The authors declare that they have no competing interests.

Subjects:

Research Funding:

NIH grants F32ES017585 (to ART-L), R01ES016366 (to MEH), R01ES015912 (to JJS)

WHOI Postdoctoral Scholar award with funding from Walter A. and Hope Noyes Smith (to ART-L)

Emory+Egelston Children’s Research Grant (to JMH)

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Endocrinology & Metabolism
  • Oxidative stress
  • Embryonic development
  • Redox
  • Antioxidant
  • Gene expression
  • Glutathione
  • Zebrafish
  • Free radicals
  • INDUCED OXIDATIVE STRESS
  • NUCLEAR GLUTATHIONE
  • ANTIOXIDANT DEFENSE
  • AXIS SPECIFICATION
  • RAT EMBRYO
  • CELL
  • ZEBRAFISH
  • MECHANISM
  • OXYGEN
  • NRF2

Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

Journal Title:

Free Radical Biology and Medicine

Volume:

Volume 65

Publisher:

, Pages 89-101

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous nonprotein antioxidant defense molecule is the tripeptide glutathione (γ-glutamylcysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0-5 days postfertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and oxidized glutathione using HPLC and calculated the whole embryo total glutathione (GSHT) concentrations and redox potentials (Eh) over 0-120 h of zebrafish development (including mature oocytes, fertilization, midblastula transition, gastrulation, somitogenesis, pharyngula, prehatch embryos, and hatched eleutheroembryos). GSHT concentration doubled between 12 h postfertilization (hpf) and hatching. The GSH Eh increased, becoming more oxidizing during the first 12 h, and then oscillated around -190 mV through organogenesis, followed by a rapid change, associated with hatching, to a more negative (more reducing) Eh (-220 mV). After hatching, Eh stabilized and remained steady through 120 hpf. The dynamic changes in GSH redox status and concentration defined discrete windows of development: primary organogenesis, organ differentiation, and larval growth. We identified the set of zebrafish genes involved in the synthesis, utilization, and recycling of GSH, including several novel paralogs, and measured how expression of these genes changes during development. Ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox state is tightly regulated early in development. This study provides a foundation for understanding the redox regulation of developmental signaling and investigating the effects of oxidative stress during embryogenesis.

Copyright information:

© 2013 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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