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Vanin-1-/- Mice Exhibit a Glutathione-Mediated Tissue Resistance to Oxidative Stress.
- Source :
- Molecular & Cellular Biology; Aug2004, Vol. 24 Issue 16, p7214-7224, 11p, 6 Graphs
- 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<subscript>5</subscript>). Here we show that Vanin-1<superscript>-/-</superscript> mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body γ-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<superscript>-/-</superscript> 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<superscript>-/-</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- OXIDATIVE stress
GLUTATHIONE
PANTOTHENIC acid
THIOLS
APOPTOSIS
CELL death
ANTIOXIDANTS
Subjects
Details
- Language :
- English
- ISSN :
- 02707306
- Volume :
- 24
- Issue :
- 16
- Database :
- Complementary Index
- Journal :
- Molecular & Cellular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 14190694
- Full Text :
- https://doi.org/10.1128/MCB.24.16.7214-7224.2004