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nicotinamide n-methyltransferase and liver diseases

Genes & Diseases 2023年第5期10卷 1883-1893页

作者： Guangyu Liang Ying Li Yan Lin Xiao Yang Jiankun Yang Shaobo Hu Anding Liu Experimental Medicine Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Hepatobiliary Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular *** n-methyltransferase(nnMT)is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pathological *** catalyzes the methylation of nicotinamide(nAM)using the universal methyl donor S-adenosyl methionine(SAM)to yield S-adeno-syl-L-homocysteine(SAH)and n1-methylnicotinamide(MnAM),directly linking methylation balance with nicotinamide adenosine dinucleotide(nAD+)*** acts on either the SAM-methylation balance or both nAD+metabolism,depending on the tissue involved or pathological settings where metabolic demand is *** physiological conditions,the liver act as an essential metabolic organ with abundant nnMT expression,while nnMT hepatic function is not mediated by its methyltransferase activity due to other major methyltransferases such as glycine n-methyltransferase(GnMT)in the ***,hepatic nnMT,as well as its metabolite is improperly regulated and linked to the worse pathological states in liver diseases,including alcoholic liver disease,non-alcoholic fatty liver disease(nAFLD),liver cirrhosis,and hepatocellular carcinoma(HCC),suggesting a potential role in the process of liver *** this review,we summarize how nnMT regulates cell methylation balance and nAD metabolism,and extensively outline the current knowledge concerning the functions of nnMT in hepatic metabolism including glucose,lipid and energy,with a specific focus on the contribution of nnMT to the pathophysiology of liver-related *** is involved in the development and progression of liver *** the complex nnMT regulatory network and its effects on pathogenesis could provide new therapeutic strategies in the context of liver diseases.

关键词： Epigenetics Liver diseases Metabolism nicotinamide n-methyltransferase non-alcoholic fatty liver disease

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nicotinamide n-methyltransferase protein expression in renal cell cancer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第2期11卷 136-143页

作者： Jun ZHAnG Xin-you XIE Su-wen YAnG Jin WAnG Chao HE Department of Clinical Laboratory Sir Run Run Show Hospital School of Medicine Zhejiang University Hangzhou 310016 China Key Laboratory of Biotherapy of Zhejiang Province Hangzhou 310016 China Department of Pathology Sir Run Run Show Hospital School of Medicine Zhejiang University ttangzhou 310016 China Biomedical Research Center Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China Department of Colorectal Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China

Objective: To understand the function of nicotinamide n-methyltransferase (nnMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant nnMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of nnMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for nnMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. nnMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of nnMT, and distant metastasis were significant prognosticators. Conclusion: nnMT is over-expressed in a large proportion in renal cell cancers. High nnMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of nnMT needs further verification in larger sample sizes.

关键词： nicotinamide n-methyltransferase Monoclonal antibody Tumor biomarker. Renal cell cancer

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