TP53 Modulates Oxidative Stress in Gata1 Erythroid Cells.

Stem Cell Reports

Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Published: February 2017

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312256PMC
http://dx.doi.org/10.1016/j.stemcr.2016.12.025DOI Listing

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