scholarly journals Alterations of methionine metabolism in hepatocarcinogenesis: the emergent role of glycine N-methyltransferase in liver injury

Author(s):  
Maria M. Simile
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Charles H. Halsted ◽  
Valentina Medici

The pathogenesis of alcoholic steatohepatitis (ASH) involves ethanol-induced aberrations in hepatic methionine metabolism that decrease levels of S-adenosylmethionine (SAM), a compound which regulates the synthesis of the antioxidant glutathione and is the principal methyl donor in the epigenetic regulation of genes relevant to liver injury. The present paper describes the effects of ethanol on the hepatic methionine cycle, followed by evidence for the central role of reduced SAM in the pathogenesis of ASH according to clinical data and experiments in ethanol-fed animals and in cell models. The efficacy of supplemental SAM in the prevention of ASH in animal models and in the clinical treatment of ASH will be discussed.


Alcohol ◽  
2002 ◽  
Vol 27 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Shelly C Lu ◽  
Hidekazu Tsukamoto ◽  
José M Mato

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
B Schiller ◽  
C Wegscheid ◽  
L Berkhout ◽  
A Zarzycka ◽  
U Steinhoff ◽  
...  
Keyword(s):  

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.


Author(s):  
Dongxiao Li ◽  
Xiangming Ding ◽  
Dean Tian ◽  
Limin Xia
Keyword(s):  

2021 ◽  
Vol 22 (14) ◽  
pp. 7249
Author(s):  
Siyer Roohani ◽  
Frank Tacke

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.


2019 ◽  
Vol 95 (6) ◽  
pp. 597-605 ◽  
Author(s):  
Yunqi An ◽  
Pengcheng Wang ◽  
Pengfei Xu ◽  
Hung-Chun Tung ◽  
Yang Xie ◽  
...  
Keyword(s):  

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