PMID:15282320

Citation	Berruyer, C, Martin, FM, Castellano, R, Macone, A, Malergue, F, Garrido-Urbani, S, Millet, V, Imbert, J, Duprè, S, Pitari, G, Naquet, P and Galland, F (2004) Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Mol. Cell. Biol. 24:7214-24
Abstract	Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1(-/-) mice is associated with an enhanced gamma-glutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1(-/-) mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.
Links	PubMed PMC479710 Online version:10.1128/MCB.24.16.7214-7224.2004
Keywords	Amidohydrolases; Animals; Apoptosis/physiology; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cell Line; Cystamine/administration & dosage; Cystamine/metabolism; Cysteamine/metabolism; Epithelial Cells/cytology; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Epithelial Cells/radiation effects; GPI-Linked Proteins; Gamma Rays; Gene Expression Regulation, Enzymologic; Glutamate-Cysteine Ligase/metabolism; Glutathione/metabolism; Herbicides/administration & dosage; Inflammation/metabolism; Mice; Mice, Inbred BALB C; Mice, Knockout; Oxidative Stress; Paraquat/administration & dosage; Promoter Regions, Genetic; Radiation-Protective Agents/metabolism; Reactive Oxygen Species/metabolism; Thymus Gland/cytology; Thymus Gland/physiology; Thymus Gland/radiation effects
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