Novel Interplay between p53 and HO-1 in Embryonic Stem Cells

Cells

Marcos Francia¹  Ayelén Toro¹  Pablo Sanchis¹  MaríaVictoria Petrone¹  Juan Bizzotto¹  Elba Vazquez¹  Valeria Levi¹  Camila Vazquez Echegaray¹  Alejandra Guberman¹  Nicolás Anselmino¹  Claudia Solari¹  Camila Oses¹ 

[1] CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina;

关键词: heme oxygenase-1;    p53;    embryonic stem cells;    gene expression regulation;   

DOI  :  10.3390/cells10010035

来源: DOAJ

【 摘 要 】

Stem cells genome safeguarding requires strict oxidative stress control. Heme oxygenase-1 (HO-1) and p53 are relevant components of the cellular defense system. p53 controls cellular response to multiple types of harmful stimulus, including oxidative stress. Otherwise, besides having a protective role, HO-1 is also involved in embryo development and in embryonic stem (ES) cells differentiation. Although both proteins have been extensively studied, little is known about their relationship in stem cells. The aim of this work is to explore HO-1-p53 interplay in ES cells. We studied HO-1 expression in p53 knockout (KO) ES cells and we found that they have higher HO-1 protein levels but similar HO-1 mRNA levels than the wild type (WT) ES cell line. Furthermore, cycloheximide treatment increased HO-1 abundance in p53 KO cells suggesting that p53 modulates HO-1 protein stability. Notably, H₂O₂ treatment did not induce HO-1 expression in p53 KO ES cells. Finally, SOD2 protein levels are also increased while Sod2 transcripts are not in KO cells, further suggesting that the p53 null phenotype is associated with a reinforcement of the antioxidant machinery. Our results demonstrate the existence of a connection between p53 and HO-1 in ES cells, highlighting the relationship between these stress defense pathways.

【 授权许可】

Unknown