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TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells.

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.

SUBMITTER: Kramer AC

PROVIDER: S-EPMC5312256 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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TP53 Modulates Oxidative Stress in Gata1<sup>+</sup> Erythroid Cells.

Kramer Ashley C AC Weber Jenna J Zhang Ying Y Tolar Jakub J Gibbens Ying Y YY Shevik Margaret M Lund Troy C TC

Stem cell reports 20170126 2

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 sensiti ...[more]

PMID: 28132886

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TP53 modulates oxidative stress in Gata1+ erythroid cells

Project description:In this report, we have found that gata1 expressing erythroid cells contribute 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 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.

2017-02-15 | GSE92754 | GEO

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Nuclear matrix protein (NRP/B) modulates the nuclear factor (Erythroid-derived 2)-related 2 (NRF2)-dependent oxidative stress response.

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Deubiquitylase USP7 regulates human terminal erythroid differentiation by stabilizing GATA1.

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