S-adenosylmethionine treatment prevents carbon tetrachloride—inducedS-adenosylmethionine synthetase inactivation and attenuates liver injury

Abstract

Administration of carbon tetrachloride to rats resulted in induction of hepatic fibrosis and a 60% reduction of hepatic S‐adenosylmethionine synthetase activity without producing any significant modification of hepatic levels of S‐adenosylmethionine synthetase messenger RNA. The reduction of S‐adenosylmethionine synthetase activity was corrected by treatment with S‐adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon tetrachloride also produced a 45% depletion of liver glutathione (reduced form) that was corrected by S‐adenosylmethionine treatment. After the rats received carbon tetrachloride, a 2.3‐fold increase in liver collagen was observed; prolyl hydroxylase activity was 2.5 times greater than that seen in controls. These increases were attenuated in animals treated with carbon tetrachloride and S‐adenosylmethionine. The attenuation by S‐adenosylmethionine treatment of the fibrogenic effect of carbon tetrachloride was associated with a decrease in the number of rats in which cirrhosis developed. (HEPATOLOGY 1992;16:1022–1027.)

Fungal S-adenosylmethionine synthetase and the control of development and secondary metabolism in Aspergillus nidulans

“…Low expression of the SAM synthetase encoding E. coli gene metK resulted in in the formation of filaments due to blocked septal ring formation (Newman et al, 1998;Wang et al, 2005). Only organisms which possess SAM feedback-inhibited SAM synthetases showed no overexpression phenotypes Corrales et al, 1992Corrales et al, , 1991Duce et al, 1988;Markham et al, 1983;Thomas and Surdin-Kerjan, 1991;Yarlett et al, 1993). The corresponding A. nidulans or S. pombe enzymes are not feedback-regulated (Hilti et al, 2000;Pieniazek et al, 1973).…”

Differential effect of thioacetamide on hepatic methionine adenosyltransferase expression in the rat

“…1 Abnormalities in hepatic MAT have long been realized in patients with various causes of cirrhosis and in several models of liver injury. 15,[32][33][34][35][36][37] Inhibition of the liver-specific MAT by 50% to 60% was felt to be the explanation for hypermethioninemia and delayed plasma clearance of methionine after intravenous injection in cirrhotic patients. 32,33,38,39 With the exception of hypoxia, in which a decreased MAT1A mRNA level was found, 35,37 all of the other examples of decreased liver-specific MAT activity reflected inactivation of the enzyme without alteration in the protein 15,16 or mRNA levels.…”

“…32,33,38,39 With the exception of hypoxia, in which a decreased MAT1A mRNA level was found, 35,37 all of the other examples of decreased liver-specific MAT activity reflected inactivation of the enzyme without alteration in the protein 15,16 or mRNA levels. 1,34,40 The molecular mechanism of the inactivation of liver-specific MAT has been recently elucidated. Modification of critical cysteine residues inactivated the enzyme by direct interference with the substrate binding site(s) or by causing dissociation of the oligomers.…”

S-adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signalingin vitro

“…AdoMet depletion has been observed in a number of experimental models of liver diseases associated with increased oxidative stress and a depletion of reduced glutathione (GSH). [21][22][23][24] Oral AdoMet treatment has therefore been used in animal models and in patients to restore GSH content in the liver with the aim to treat liver diseases. [25][26][27] We were interested in AdoMet not because of its role in GSH biosynthesis, 28,29 but because PRMT1 uses AdoMet as the methyl group donor for STAT1 methylation (Fig.…”