Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering arrest in G1 phase of the cell cycle

Karoline C. Manthey, Rocio Rodriguez-Melendez, Jia Tse Hoi, Janos Zempleni

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Eukaryotes convert riboflavin to flavin adenine dinucleotide, which serves as a coenzyme for glutathione reductase and other enzymes. Glutathione reductase mediates the regeneration of reduced glutathione, which plays an important role in scavenging free radicals and reactive oxygen species. Here we tested the hypothesis that riboflavin deficiency decreases glutathione reductase activity in HepG2 liver cells, causing oxidative damage to proteins and DNA, and cell cycle arrest. As a secondary goal, we determined whether riboflavin deficiency is associated with gene expression patterns indicating cell stress. Cells were cultured in riboflavin-deficient and riboflavin-supplemented media for 4 days. Activity of glutathione reductase was not detectable in cells cultured in riboflavin-deficient medium. Riboflavin deficiency was associated with an increase in the abundance of damaged (carbonylated) proteins and with increased incidence of DNA strand breaks. Damage to proteins and DNA was paralleled by increased abundance of the stress-related transcription factor GADD153. Riboflavin-deficient cells arrested in G1 phase of the cell cycle. Moreover, oxidative stress caused by riboflavin deficiency was associated with increased expression of clusters of genes that play roles in cell stress and apoptosis. For example, the abundance of the pro-apoptotic pleiomorphic adenoma gene-like 1 gene was 183% greater in riboflavin-deficient cells compared with riboflavin-sufficient controls. We conclude that riboflavin deficiency is associated with oxidative damage to proteins and DNA in liver cells, leading to cell stress and G1 phase arrest.

Original languageEnglish (US)
Pages (from-to)250-256
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume17
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Cell cycle
  • DNA damage
  • Gene expression
  • Protein carbonylation
  • Riboflavin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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