TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells

Ashley C. Kramer, Jenna Weber, Ying Zhang, Jakub Tolar, Ying Y. Gibbens, Margaret Shevik, Troy C. Lund

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant proportion of total-body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with a mutation in its DNA-binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS) and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell-cycle regulator, has additional roles in controlling cellular oxidative stress.

Original languageEnglish (US)
Pages (from-to)360-372
Number of pages13
JournalStem Cell Reports
Volume8
Issue number2
DOIs
StatePublished - Feb 14 2017

Bibliographical note

Funding Information:
We gratefully thank the laboratory of Dr. Zon for sharing the vlad tepes zebrafish. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the NIH under award number K08HL108998 (T.C.L.), ASH Junior Faculty Scholar Award (T.C.L.), the University of Minnesota Academic Health Center Seed Grant (T.C.L.), The Children's Cancer Research Fund (T.C.L.), and The Viking's Research Fund (T.C.L.).

Publisher Copyright:
© 2017 The Authors

Keywords

  • erythroid precursors
  • mitochondria
  • oxidative stress
  • reactive oxygen species
  • tp53
  • zebrafish

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