Glutathione and p53 independently mediate responses against oxidative stress in ES cells

Coe, Jonathan P, Rahman, Irfan, Sphyris, Nathalie, Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X and Harrison, David J. 2002. Glutathione and p53 independently mediate responses against oxidative stress in ES cells. Free Radical Biology and Medicine 32 (2) , pp. 187-196. 10.1016/S0891-5849(01)00792-4

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Abstract

We have investigated the roles of the antioxidant glutathione and p53 in the response of embryonic stem (ES) cells to oxidative stress. ES cells express γGCS, a critical enzyme in glutathione (GSH) biosynthesis. Treatment with the pro-oxidant menadione led to elevation of GSH, a strong apoptotic response and reduced clonogenic survival. Addition of BSO, a specific γGCS inhibitor depleted GSH pools and prevented the menadione-induced increase in GSH, sensitizing cells to oxidative insult. Although p53 status had no bearing on either the basal levels of GSH or the menadione-induced GSH response, the levels of menadione-induced apoptosis were reduced in the absence of p53. We conclude that the pathways involving p53 and GSH act independently to protect against the deleterious effects of oxidative damage. Furthermore, the presence of an intact p53 pathway confers a long-term growth advantage post oxidative stress. Thus, in the absence of p53 ES cells bearing genotoxic damage are less likely to be propagated, suggesting that p53-dependent apoptosis acts to limit the deleterious effects of oxidative stress during early development.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	GSH; p53; apoptosis; ROS; ES cells; free radicals.
Publisher:	Elsevier
ISSN:	0891-5849
Last Modified:	25 Oct 2022 10:11
URI:	https://orca.cardiff.ac.uk/id/eprint/61376

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