TP53 modulates oxidative stress in Gata1+ erythroid cells

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. Overall design: We performed RNA-seq in two experiments. (1) Wild-type zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group). (2) tp53 mutant zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group).

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Kramer AC, Weber J, Zhang Y, Tolar J, Gibbens YY, Shevik M, Lund TC