RESUMO
The objective of this study was to clarify the relationship between the accumulation of S-adenosylhomocysteine (SAH) and the change in the SAH hydrolase activity in vitamin B6 (B6). Male Wistar rats were fed a control diet (control and pair-fed groups) or B6-free diet (B6-deficient group) for 5 wk. Although the SAH-synthetic activity of SAH hydrolase significantly increased in the B6-deficient group, SAH-hydrolytic activity of SAH hydrolase showed no significant difference in the liver among the three groups. On the other hand, SAH hydrolase mRNA in the liver did not show any significant change. Thus, the accumulation of SAH would be due to the increased SAH-synthetic activity of SAH hydrolase. The disturbed methionine metabolism by B6-deficiency, such as a significant increase of plasma homocysteine, might induce the activation of SAH hydrolase in the direction of SAH synthesis.
Assuntos
Adenosil-Homocisteinase/metabolismo , Metionina/metabolismo , S-Adenosil-Homocisteína/metabolismo , Deficiência de Vitaminas do Complexo B/metabolismo , Análise de Variância , Animais , Peso Corporal/fisiologia , Homocisteína/sangue , Fígado/enzimologia , Fígado/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Deficiência de Vitaminas do Complexo B/sangue , Deficiência de Vitaminas do Complexo B/enzimologiaRESUMO
The objective of this study was to examine how transient high plasma homocysteine (Hcy) levels affect the metabolism of Hcy, the activity and expression of S-adenosylhomocysteine (SAH) hydrolase which catalyzes both SAH hydrolysis and SAH synthesis. Wistar ST rats (males) were cannulated in the right jugular vein for intravenous infusion of physiological saline or DL-Hcy solutions (15 and 30 mg/mL) for 1 h at 1.1 mL/h/rat. The content of S-adenosylmethionine (SAM), SAH-synthetic activity of SAH hydrolase and the expression of SAH hydrolase mRNA in liver extracts showed no significant difference in the Hcy infused groups as compared to the Control group. On the other hand, the contents of hepatic SAH in the Hcy infused groups were dose-dependent and significantly higher than that of the Control group. Thus, this study showed that hepatic SAH increased without any increase in the SAH-synthetic activity and the expression of SAH hydrolase mRNA under transient high plasma Hcy levels after intravenous infusion of Hcy.
Assuntos
Adenosil-Homocisteinase/metabolismo , Homocisteína/sangue , Homocisteína/farmacologia , S-Adenosil-Homocisteína/metabolismo , Adenosil-Homocisteinase/efeitos dos fármacos , Adenosil-Homocisteinase/genética , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Homocisteína/administração & dosagem , Infusões Intravenosas/métodos , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , S-Adenosilmetionina/sangue , Cloreto de Sódio/administração & dosagemRESUMO
Recently we reported that the supplementation of vitamin B6 to low vitamin B6 diet caused suppression in colon tumorigenesis and cell proliferation of azoxymethane-treated mice in a dose-dependent manner among 1, 7, and 14 mg pyridoxine HCl/kg diet (J. Nutr. 131: 2204-2207, 2001). To examine the mechanism of the anticolon tumor effect of vitamin B6, male ICR mice were fed the diet containing 1, 7, 14, and 35 mg pyridoxine HCl/kg diet for 22 wk and simultaneously given a weekly injection of azoxymethane for an initial 10 wk. The supplementation of vitamin B6 to a low vitamin B6 diet (1 mg pyridoxine HCl/kg) suppressed the levels of colonic 8-hydroxyguanosine and 4-hydroxynonenal and inducible nitric oxide synthase protein. The results suggest that the preventive effect of vitamin B6 against colon tumorigenesis is at least in part mediated by reducing oxidative stress and nitric oxide production.