| First Author | Berruyer C | Year | 2004 |
| Journal | Mol Cell Biol | Volume | 24 |
| Issue | 16 | Pages | 7214-24 |
| PubMed ID | 15282320 | Mgi Jnum | J:92268 |
| Mgi Id | MGI:3052282 | Doi | 10.1128/MCB.24.16.7214-7224.2004 |
| Citation | Berruyer C, et al. (2004) Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Mol Cell Biol 24(16):7214-24 |
| abstractText | 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. |
