The multi-functional roles of GNMT in toxicology and cancer

Chia Hung Yen, Yu Ting Lin, Heng Li Chen, Shih Yin Chen, Yi Ming Arthur Chen

研究成果: 雜誌貢獻回顧型文獻

25 引文 斯高帕斯(Scopus)

摘要

Although glycine N-methyltransferase (GNMT) has been discovered for five decades, its function was not elucidated until recently. In this review, we discuss the multiple roles of GNMT in toxicology and cancer. Besides catalyzing the production of methylglycine (sarcosine) in one carbon metabolism pathway, GNMT was found to be able to bind a number of polycyclic aromatic hydrocarbons and inhibit DNA adducts formation. Moreover, GNMT exerts protective effects against the cytotoxicity and carcinogenicity of benzo(a)pyrene and aflatoxin B1 in vitro and in vivo. Occupational study showed that workers who had genotypes with higher GNMT promoter activity may have lower content of oxidative damaged DNA products in their urine. In terms of cancer, recent studies using GNMT knockout mouse models demonstrated that GNMT deficiency has high penetrance in inducing the development of steatohepatitis and hepatocellular carcinoma. In terms of the mechanism, besides dysregulation of epigenetic modification, insights have been provided by recent identification of two novel proteins interacting with GNMT-DEPTOR and NPC2. These studies suggest that GNMT not only is involved in mTOR signaling pathway, but also plays an important role in the intracellular trafficking of cholesterol. The implication of these findings to the preventive medicine and translational research will be discussed.
原文英語
頁(從 - 到)67-75
頁數9
期刊Toxicology and Applied Pharmacology
266
發行號1
DOIs
出版狀態已發佈 - 一月 1 2013
對外發佈Yes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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