title: 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.
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Kramer
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Weber
authors.affiliation: Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Gibbens
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Shevik
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: lundx072@umn.edu.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D050982:GATA1 Transcription Factor; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53
keywords: erythroid precursors; mitochondria; oxidative stress; reactive oxygen species; tp53; zebrafish