Deficiency of glycine N-methyltransferase results in deterioration of cellular defense to stress in mouse liver

Yi Jen Liao, Kuan Hsuan Chen, Shiu Feng Huang, Tzu Lang Chen, Chung Kwe Wang, Chau Heng Chien, Ting Fen Tsai, Shih Ping Liu, Yi Ming Arthur Chen

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Purpose: Previously, we reported that glycine N-methyltransferase (GNMT) interacts with benzo[a]pyrene (BaP) and inhibits BaP-DNA adducts formation. In addition, Gnmt knockout (Gnmt-/-) mice developed chronic hepatitis and hepatocellular carcinoma (HCC). The aims of this study were to understand the gene expression profile of Gnmt-/- mice and to study the interaction between BaP and GNMT deficiency in vivo. Experimental design: Gene expression profiles of Gnmt-/- mice were analyzed by 2-D PAGE and real-time PCR. Both wild-type and Gnmt-/- mice were challenged with BaP and sacrificed at the age of 13 months. Results: Compared with the wild-type mice, proteins involved in the anti-oxidation/detoxification response, glycolytic energy metabolism and one-carbon metabolism pathways were down-regulated significantly in Gnmt-/- mice. Malondialdehyde assay showed that lipid peroxidation was significantly increased in the Gnmt-/- mice liver. H2O2 treatment demonstrated that the survival rate of HuH-7 cells overexpressing GNMT was significantly higher than the controls. BaP challenge experiments showed that 71.4% (5/7) of male and all (7/7) female Gnmt -/- mice developed HCC, while only 16.7% (1/6) of male and 20% (1/5) of female wild-type mice had HCC. Conclusion and clinical relevance: GNMT regulates genes related to detoxification and antioxidation pathways. BaP is a liver cancer carcinogen especially during GNMT deficiency.

Original languageEnglish
Pages (from-to)394-406
Number of pages13
JournalProteomics - Clinical Applications
Volume4
Issue number4
Publication statusPublished - Apr 2010
Externally publishedYes

Keywords

  • Anti-oxidation
  • Benzo[a]pyrene
  • Detoxification
  • Glycine N-methyltransferase
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Clinical Biochemistry

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