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Vanin-1(-/-) mice show decreased NSAID- and Schistosoma-induced intestinal inflammation associated with higher glutathione stores.
Martin, Florent; Penet, Marie-France; Malergue, Fabrice; Lepidi, Hubert; Dessein, Alain; Galland, Franck; de Reggi, Max; Naquet, Philippe; Gharib, Bouchra.
Afiliação
  • Martin F; Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale, Universté de la Méditerranée, Marseille, France.
J Clin Invest ; 113(4): 591-7, 2004 Feb.
Article em En | MEDLINE | ID: mdl-14966568
Vanin-1 is a membrane-anchored pantetheinase highly expressed in the gut and liver. It hydrolyzes pantetheine to pantothenic acid (vitamin B5) and the low-molecular-weight thiol cysteamine. The latter is believed to be a key regulating factor of several essential metabolic pathways, acting through sulfhydryl-disulfide exchange reactions between sulfhydryl groups of the enzymes and the oxidized form, cystamine. Its physiological importance remains to be elucidated, however. To explore this point, we developed Vanin-1-deficient mice that lack free cysteamine. We examined the susceptibility of deficient mice to intestinal inflammation, either acute (NSAID administration) or chronic (Schistosoma infection). We found that Vanin-1(-/-) mice better controlled inflammatory reaction and intestinal injury in both experiments. This protection was associated with increased gamma-glutamylcysteine synthetase activity and increased stores of reduced glutathione, as well as reduced inflammatory cell activation in inflamed tissues. Oral administration of cystamine reversed all aspects of the deficient phenotype. These findings suggest that one cysteamine function is to upregulate inflammation. Consequently, the pantetheinase activity of Vanin-1 molecule could be a target for a new anti-inflammatory strategy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Schistosoma mansoni / Esquistossomose mansoni / Moléculas de Adesão Celular / Anti-Inflamatórios não Esteroides / Indometacina / Glutationa / Inflamação / Intestinos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Schistosoma mansoni / Esquistossomose mansoni / Moléculas de Adesão Celular / Anti-Inflamatórios não Esteroides / Indometacina / Glutationa / Inflamação / Intestinos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article