PUBLICATION
TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells.
- Authors
- Kramer, A.C., Weber, J., Zhang, Y., Tolar, J., Gibbens, Y.Y., Shevik, M., Lund, T.C.
- ID
- ZDB-PUB-170131-4
- Date
- 2017
- Source
- Stem Cell Reports 8(2): 360-372 (Journal)
- Registered Authors
- Lund, Troy
- Keywords
- erythroid precursors, mitochondria, oxidative stress, reactive oxygen species, tp53, zebrafish
- Datasets
- GEO:GSE92754
- MeSH Terms
-
- Animals
- Cell Death/genetics
- Erythroid Cells/cytology
- Erythroid Cells/metabolism*
- GATA1 Transcription Factor/genetics*
- GATA1 Transcription Factor/metabolism
- Gene Knockout Techniques
- Gene Silencing
- Mice
- Mitochondria/genetics
- Mitochondria/metabolism
- Oxidation-Reduction
- Oxidative Stress*/genetics
- Reactive Oxygen Species/metabolism
- Tumor Suppressor Protein p53/genetics*
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- PubMed
- 28132886 Full text @ Stem Cell Reports
Citation
Kramer, A.C., Weber, J., Zhang, Y., Tolar, J., Gibbens, Y.Y., Shevik, M., Lund, T.C. (2017) TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells.. Stem Cell Reports. 8(2):360-372.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping