Effect of n-3 polyunsaturated fatty acid on gene expression of the critical enzymes involved in homocysteine metabolism

Nutr J. 2012 Jan 19;11:6. doi: 10.1186/1475-2891-11-6.

Abstract

Background: Previous studies showed that plasma n-3 polyunsaturated fatty acid (PUFA) was negatively associated with plasma homocysteine (Hcy).

Objective: We investigated the regulatory effect of n-3 PUFA on mRNA expression of the critical genes encoding the enzymes involved in Hcy metabolism.

Methods: HepG2 cells were treated with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA) respectively for 48 h. The cells were collected and total RNA was isolated. The mRNA expression levels of the genes were determined by using Real Time-PCR.

Results: Compared with controls, the mRNA expression levels of 5-methyltetrahydrofolate reductase (MTHFR) were significantly increased in the DHA group (p < 0.05) and ALA group (p < 0.05); Significantly down-regulated mRNA expression of methionine adenosyltransferase (MAT) was observed with the treatments compared with the controls; the level of MAT expression was significant lower in the DHA group than the ALA group (p < 0.05); Cystathionine-γ-lyase (CSE) expression was significantly increased in the DHA (p < 0.05) and EPA groups (p < 0.05) compared with control. No significant changes were shown in mRNA expression levels of S-adenosylhomocysteine hydrolases (SAHH), cystathionine β-synthase (CBS), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR).

Conclusions: Our results suggest that DHA up-regulates CSE and MTHFR mRNA expression and down-regulates MAT mRNA expression involved in Hcy metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystathionine gamma-Lyase / genetics*
  • Docosahexaenoic Acids / pharmacology
  • Down-Regulation / drug effects*
  • Eicosapentaenoic Acid / pharmacology
  • Fatty Acids, Omega-3 / pharmacology*
  • Gene Expression / drug effects*
  • Hep G2 Cells
  • Homocysteine / genetics
  • Homocysteine / metabolism*
  • Humans
  • Liver / enzymology
  • Methionine Adenosyltransferase / genetics*
  • RNA, Messenger / analysis
  • Up-Regulation / drug effects
  • alpha-Linolenic Acid / pharmacology

Substances

  • Fatty Acids, Omega-3
  • RNA, Messenger
  • Homocysteine
  • alpha-Linolenic Acid
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Methionine Adenosyltransferase
  • Cystathionine gamma-Lyase