Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering arrest in G1 phase of the cell cycle
| Autor: | Jia Tse Hoi, Rocio Rodriguez-Melendez, Janos Zempleni, Karoline C. Manthey |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
DNA damage
Endocrinology Diabetes and Metabolism Clinical Biochemistry Glutathione reductase Riboflavin Biology medicine.disease_cause Biochemistry Article Cell Line Protein Carbonylation chemistry.chemical_compound Riboflavin Deficiency medicine Humans heterocyclic compounds Molecular Biology Oligonucleotide Array Sequence Analysis Flavin adenine dinucleotide Nutrition and Dietetics Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology G1 Phase Proteins food and beverages Glutathione Cell cycle Molecular biology Oxidative Stress Glutathione Reductase Liver chemistry Cell culture human activities Transcription Factor CHOP Oxidative stress DNA Damage |
| Zdroj: | The Journal of Nutritional Biochemistry. 17:250-256 |
| ISSN: | 0955-2863 |
| DOI: | 10.1016/j.jnutbio.2005.05.004 |
| Popis: | 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 four 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. |
| Databáze: | OpenAIRE |
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