S‐adenosylmethionine inhibits la ribonucleoprotein domain family member 1 in murine liver and human liver cancer cells

Abstract

Background and Aims: Methionine adenosyltransferase 1A (MAT1A) is responsible for S-adenosylmethionine (SAMe) biosynthesis in the liver. Mice lacking Mat1a have hepatic SAMe depletion and develop NASH and HCC spontaneously. Several kinases are activated in Mat1a knockout (KO) mice livers. However, characterizing the phospho-proteome and determining whether they contribute to liver pathology remain open for study. Our study aimed to provide this knowledge. Approach and Results:We performed phospho-proteomics in Mat1a KO mice livers with and without SAMe treatment to identify SAMe-dependent changes that may contribute to liver pathology. Our studies used Mat1a KO mice at different ages treated with and without SAMe, cell lines, in vitro translation and kinase assays, and human liver specimens. We found that the most striking change was hyperphosphorylation and increased content of Real-time RT-PCRTotal RNA was subjected to real-time RT-PCR using a published protocol. [22] See the Supporting Information Supplemental Methods for details. Western blottingTotal protein from cells or tissues was subjected to western blotting [21] with antibodies (Table S1). Images were quantified by densitometry using the ImageJ densitometry program (

AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease

“…The phosphorylation state regulates mRNA translation and subsequent ribosome biogenesis [55]. Increased phosphorylation of Larp1 is responsible for the progression of nonalcoholic steatohepatitis and hepatocellular carcinoma [56]. Phosphorylation of Larp1 by PTEN-induced kinase 1 (PINK1) disrupted mitochondrial local protein synthesis and reduced mtDNA replication [57].…”

“…Larp1 expression was upregulated in the glomeruli of diabetic rats (Figure 6A-B), similar to HG-treated podocytes (Figure 6C-D). There is a correlation between the phosphorylation of Larp1 and its molecular activity [25]. Therefore, we further measured the level of phosphorylated Larp1.…”

Hepatocellular Carcinoma Chemoprevention with Generic Agents

“…Depletion of SAMe by Mat1a knockout leads to HCC development in NAFLD mouse model. 96 In a phase II trial in 87 HCV cirrhosis patients, SAMe did not change serum AFP level and biomarkers of liver injury and oxidative stress. 97 Phytochemicals, e.g., curcumin (turmeric extract), resveratrol (polyphenol in grapes, red wine, and berries), silymarin (herbal flavonoid), and carotenoids, have been studied as potential HCC chemoprevention agents that modulate various molecular pathways involved in oncogenesis and cytoprotective mechanisms in pre-clinical models.…”

“…Depletion of SAMe by Mat1a knockout leads to HCC development in NAFLD mouse model. 96 In a phase II trial in 87 HCV cirrhosis patients, SAMe did not change serum AFP level and biomarkers of liver injury and oxidative stress. 97…”

Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy

“…Phosphorylation of plectin-1 (phospho-Ser-4253) and α-HS-glycoprotein (phospho-Ser 138 and 312) were also found to be potential HCC biomarkers ( 84 ). Furthermore, phosphorylation of la-related protein 1 (LARP1)-T449 and mothers against decapentaplegic homolog 2/3 (Smad2/3)-Thr8 could be useful for HCC detection ( 78 , 80 ).…”