Cystathionine beta synthase deficiency induces catalase-mediated hydrogen peroxide detoxification in mice liver.
Cystathionine beta synthase deficiency induces hyperhomocysteinemia which is considered as a risk factor for vascular diseases. Studies underlined the importance of altered cellular redox reactions in hyperhomocysteinemia-induced vascular pathologies. Nevertheless, hyperhomocysteinemia also induces hepatic dysfunction which may accelerate the development of vascular pathologies by modifying cholesterol homeostasis. The aim of the present study was to analyze the modifications of redox state in the liver of heterozygous cystathionine beta synthase-deficient mice, a murine model of hyperhomocysteinemia. In this purpose, we quantified levels of reactive oxygen and nitrogen species and we assayed activities of main antioxidant enzymes. We found that cystathionine beta synthase deficiency induced NADPH oxidase activation. However, there was no accumulation of reactive oxygen (superoxide anion, hydrogen peroxide) and nitrogen (nitrite, peroxynitrite) species. On the contrary, hepatic hydrogen peroxide level was decreased independently of an activation of glutathione-dependent mechanisms. In fact, cystathionine beta synthase deficiency had no effect on glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. However, we found a 50% increase in hepatic catalase activity without any variation of expression. These findings demonstrate that cystathionine beta synthase deficiency initiates redox disequilibrium in the liver. However, the activation of catalase attenuates oxidative impairments.
EA 3508, Université Paris Diderot - Paris 7, Paris, France.
Julien
J
Hamelet
Virginie
V
Seltzer
Emile
E
Petit
Christophe
C
Noll
Karine
K
Andreau
Jean M
JM
Delabar
Nathalie
N
Janel
D000818:Animals; D001483:Base Sequence; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006712:Homocystinuria / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D017931:DNA Primers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D006861:Hydrogen Peroxide; D002374:Catalase; D051547:Heme Oxygenase-1; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; D003541:Cystathionine beta-Synthase