Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein |
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Authors: | Catherine Aude-Garcia Christian Villiers Serge M. Candéias Catherine Garrel Caroline Bertrand Véronique Collin Patrice N. Marche Evelyne Jouvin-Marche |
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Affiliation: | 1.CEA, DSV, iRTSV, Laboratoire Biochimie et Biophysique des Systèmes Intégrés,Grenoble Cedex 9,France;2.CNRS, UMR 5092,Grenoble,France;3.Université Joseph Fourier,Grenoble,France;4.INSERM U823, Institut Albert Bonniot,Grenoble,France;5.Département de Biochimie-Toxicologie-Pharmacologie,Centre Hospitalier Universitaire de Grenoble,Grenoble,France |
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Abstract: | The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrPC is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP−/− thymocytes display a higher susceptibility to H2O2 exposure than PrP+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP−/− thymocytes are more sensitive to oxidative stress. PrPC function appears to be specific for oxidative stress, since no significant differences are observed between PrP−/− and PrP+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrPC a protective function in thymocytes against oxidative stress. |
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