Differential expression of S-adenosylmethionine synthetase isozymes in different cell types of rat liver

Abstract

methylation reactions in vivo and also serves the propylMammalian S-adenosylmethionine (AdoMet) synthetase examino donor in polyamine biosynthesis. AdoMet synthetase ists as two isozymes, liver-type and nonhepatic-type enzymes, exists as two isozymes, liver-type and nonhepatic-type enwhich are the products of two different genes. It is known that zymes, respectively. The liver-type isozyme is confined to the liver-type isozyme is only expressed in adult liver. Whereas, the liver, whereas the nonhepatic-type isozyme is widely disthe nonhepatic-type isozyme is widely distributed in various tributed in various tissues examined and faintly detected in tissues. In addition to the liver-type isozyme, a minor amount adult liver. [2][3][4][5][6][7][8] We have recently reported that the nonhepaticof the nonhepatic-type isozyme is also detected in adult liver. To investigate the distribution of these two isozymes in the type isozyme messenger RNA (mRNA) predominantly exists liver in detail, the localization of these two isozymes was exam-in fetal human liver and is replaced by the liver-type isozyme ined in each cell type of liver using a combination of cell mRNA during development. 9 In addition, we have also refractionation technique and Western blot analysis. In the paren-ported that the nonhepatic-type isozyme mRNA is obviously chymal cells, the liver-type isozyme protein was predominantly induced by 3-methyl-4-dimethylaminoazobenzene adminisexpressed, and a small amount of the nonhepatic-type isozyme tration as a carcinogen in adult rat livers.10 From these results protein was also detected. On the other hand, in the stellate we proposed that the nonhepatic-type isozyme seemed to be cells the nonhepatic-type isozyme protein was exclusively or an oncodevelopmental marker in the hepatocarcinogenesis. only expressed. Interestingly, a large amount of both isozymes However, these results were obtained from whole liver tiswere present in endothelial and Kupffer cell fraction. Using sues. Particularly, in the case of tumor tissues we could not both antibodies to anti-rat nonhepatic-type and liver-type iso-exclude the possibility that specimens of hepatomas used zymes, respectively, immunohistochemical analysis clearly con-contained normal parts near the tumor region. In addition, firmed these results. In addition, in cultured hepatocellular liver tissue is mainly composed of several cell types, parencarcinoma cells (FAA-HTC1), the nonhepatic-type isozyme pro-chymal cells (hepatocytes), endothelial cells, Kupffer cells, tein only was detected, and the liver-type isozyme protein com-pit cells, and stellate cells (fat-storing cells, Ito cells, or lipopletely disappeared. This result indicates that the changes in cytes). Therefore, it seems of particular interest to clarify the the isozyme expression is regulated within the parenchymal localization of these two isozymes in normal rat liver using cells. Administration of hepatotoxic drug carbon tetrachloride more appropriate methods. (CCl 4 ) to rats resulted in about 40% to 50%...

Role of Methionine Adenosyltransferase α2 and β Phosphorylation and Stabilization in Human Hepatic Stellate Cell Trans‐Differentiation

“…We and others have shown that the activity of the MATII enzyme composed of MATα2 and MATβ subunits is decreased during HSC activation despite an induction of MAT genes (Shimizu-Saito et al, 1997; Ramani et al, 2010) leading to a drop in SAMe levels and global DNA hypomethylation (Ramani et al, 2010) promoting HSC activation. Our mutation analysis shows that whereas the MATα2-P1 and P2 mutants (Table 1) do exhibit reduced binding to MATβ, they still promote HSC activation.…”

S-Adenosylmethionine Blocks Collagen I Production by Preventing Transforming Growth Factor-β Induction of the COL1A2 Promoter

“…Metabolites of AdoMet, such as SAH and MTA, and methionine, a precursor of AdoMet, were used at 30 M and found to decrease collagen I protein and COL1A1 and COL1A2 mRNA levels in HSC (Fig. 4, C and D); however, the effects mediated by methionine were lower compared with those of the other treatments perhaps because of the extremely low expression of methionine adenosyltransferase 1A in HSC (36).…”

“…Furthermore, two metabolites of AdoMet, SAH and MTA, were able to replicate these same effects at the protein and mRNA level. Methionine, an AdoMet precursor, also lowered collagen I protein and mRNA although less effectively, probably because of the minimal methionine adenosyltransferase 1A activity in HSC (36). Because SAH and MTA, unlike AdoMet, are not methylating agents, unless they generate AdoMet again, it is likely that the down-regulation of collagen I protein and mRNA by AdoMet may not be the result of gene silencing via methylation.…”

Correlation between the expression of methionine adenosyltransferase and the stages of human colorectal carcinoma

“…We reported previously that in the kidney, MAT II was mainly localized in the distal tubules 17 and in the liver, MAT II was only expressed in the hepatic stellate cells. 18 The T/N ratio in the colon of our patient 3 was very high. This patient was diagnosed as having a villous tumor which is known to have high secreting activity.…”