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Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2004 Aug; Vol. 24 (16), pp. 7214-24. - Publication Year :
- 2004
-
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.
- Subjects :
- Amidohydrolases
Animals
Apoptosis physiology
Cell Adhesion Molecules genetics
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
Herbicides administration & dosage
Inflammation metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Paraquat administration & dosage
Promoter Regions, Genetic
Radiation-Protective Agents metabolism
Reactive Oxygen Species metabolism
Thymus Gland cytology
Thymus Gland physiology
Thymus Gland radiation effects
Cell Adhesion Molecules metabolism
Glutathione metabolism
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 24
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 15282320
- Full Text :
- https://doi.org/10.1128/MCB.24.16.7214-7224.2004