TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671116303150 |
| _version_ | 1818062092361531392 |
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| author | Ashley C. Kramer Jenna Weber Ying Zhang Jakub Tolar Ying Y. Gibbens Margaret Shevik Troy C. Lund |
| author_facet | Ashley C. Kramer Jenna Weber Ying Zhang Jakub Tolar Ying Y. Gibbens Margaret Shevik Troy C. Lund |
| author_sort | Ashley C. Kramer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T13:58:43Z |
| format | Article |
| id | doaj.art-d50f6deca1e14e6a8e2eb65894f9edd0 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-10T13:58:43Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-d50f6deca1e14e6a8e2eb65894f9edd02022-12-22T01:45:52ZengElsevierStem Cell Reports2213-67112017-02-018236037210.1016/j.stemcr.2016.12.025TP53 Modulates Oxidative Stress in Gata1+ Erythroid CellsAshley C. Kramer0Jenna Weber1Ying Zhang2Jakub Tolar3Ying Y. Gibbens4Margaret Shevik5Troy C. Lund6Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USAMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USAMetabolism 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.http://www.sciencedirect.com/science/article/pii/S2213671116303150erythroid precursorsoxidative stresstp53zebrafishreactive oxygen speciesmitochondria |
| spellingShingle | Ashley C. Kramer Jenna Weber Ying Zhang Jakub Tolar Ying Y. Gibbens Margaret Shevik Troy C. Lund TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells Stem Cell Reports erythroid precursors oxidative stress tp53 zebrafish reactive oxygen species mitochondria |
| title | TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells |
| title_full | TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells |
| title_fullStr | TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells |
| title_full_unstemmed | TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells |
| title_short | TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells |
| title_sort | tp53 modulates oxidative stress in gata1 erythroid cells |
| topic | erythroid precursors oxidative stress tp53 zebrafish reactive oxygen species mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S2213671116303150 |
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