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Linking the pro‐oxidant influences of epigallocatechin gallate (EGCG) to intestinal cholesterol metabolism via alterations in sirtuin 1 (SIRT1) using Caco‐2 cells
Author(s) -
Wegner Casey J,
Kim Bohkyung,
Yang Yue,
Park Youngki,
Koo Sung I,
Lee Jiyoung
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.361.8
Subject(s) - caco 2 , sterol regulatory element binding protein , mitochondrial biogenesis , downregulation and upregulation , cholesterol , chemistry , sirtuin , liver x receptor , hmg coa reductase , sirtuin 1 , lipid metabolism , biochemistry , nuclear receptor , microbiology and biotechnology , mitochondrion , reductase , biology , sterol , cell , transcription factor , enzyme , nad+ kinase , gene
The intestine has emerged as a dynamic regulator of whole body cholesterol homeostasis. Pro‐oxidant effects by phenolics may influence intestine‐specific cholesterol regulation. In this study, we link the pro‐oxidant nature of EGCG to its effects on intestinal cholesterol metabolism using Caco‐2 cells. Significant and sustained (0.5–1.5 h) increases in H2O2 formation were observed after EGCG additions to culture media in the absence of cells. This corresponded to a significant increase in reactive oxygen species in Caco‐2 cells after 9 h EGCG treatments (100 μM). EGCG treatments at 50 and 100 μM concentrations decreased mitochondrial DNA copy numbers, which may reflect mitochondrial oxidative damage and/or decreased mitochondrial biogenesis. Nuclear content of SIRT1, a protein deacetylase critically involved in mitochondrial biogenesis, was altered following EGCG treatments. SIRT1 has also been shown to directly deacetylate sterol regulatory element binding protein 2 (SREBP‐2), subsequently reducing SREBP‐2 transcriptional activity. Accordingly, SREBP‐2 target genes, i.e. LDL receptor protein and HMG‐CoA reductase, were upregulated in differentiated Caco‐2 cells after 100 μM EGCG treatments. These results suggest that EGCG‐driven pro‐oxidant effects may alter intestinal cholesterol metabolism by regulating SREBP‐2 activity via SIRT1 inhibition or redistribution. Grant Funding Source : USDA Hatch