Differential effects of dietary fatty acids on the regulation of CYP2E1 and protein kinase C in human hepatoma HepG2 cells

Mikyung Sung, Ikhwan Kim, Miyoung Park, Youngmi Whang, Myoungsook Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

We investigated the effects of different fatty acids (FAs) or with different degrees of unsaturation on cytochrome P450 2E1 (CYP2E1) induction and protein kinase C (PKC) activity in human hepatoma HepG2 cells. As the degree of unsaturation increased, the cell survival rate decreased for FAs with 18 carbons, but linolenic acid (LNA) or docosahexaenoic acid (DHA) groups were similar even through they have different degrees of unsaturation. Treatment with palmitic acid (PA), oleic acid (OA), linoleic acid (LA), LNA, and DHA resulted in respective cellular FA concentrations of C16:0 (43.1%), C18:1 (18.5%), C18:2 (7.4%), LNA (2.85%), and C22:6 (3.13%), which was highest for the FA that was used as the treatment, indicating that their incorporation within the cell is directly proportional to treatment. After 2 hours of cultivation, the lipid peroxide (LPO) in the DHA group increased 600% compared with control, and was much higher than in the groups treated with the other FAs, with LNA > LA > OA > PA. CYP2E1 induction increased with greater effect as the degree of unsaturation of OA, LA, and DHA increased. PA did not affect PKC activity, but DHA treatment increased PKC activity the most. The effects of LNA and LA were similar, but less than that of DHA, and that of OA was lower still, indicating that activity of PKC is proportional to the degree of unsaturation, and not the configuration of the FA. Increased plasma membrane concentrations of n-3 FA, such as DHA, might exert regulatory effects on PKC by increasing membrane fluidity, causing changes in CYP2E1, elevating levels of LPO, or producing oxidative stress.

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalJournal of Medicinal Food
Volume7
Issue number2
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • Cytochrome P450 2E1
  • Docosahexaenoic acid
  • Lipid peroxides
  • Polyunsaturated fatty acids
  • Protein kinase C

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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