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Alpha-oxoglutarate inhibits the proliferation of immortalized normal bladder epithelial cells via an epigenetic switch involving ARID1A
- Title
- Alpha-oxoglutarate inhibits the proliferation of immortalized normal bladder epithelial cells via an epigenetic switch involving ARID1A
- Authors
- Shahid M.; Gull N.; Yeon A.; Cho E.; Bae J.; Yoon H.S.; You S.; Yoon H.; Kim M.; Berman B.P.; Kim J.
- Ewha Authors
- 윤하나; 윤현석
- SCOPUS Author ID
- 윤하나; 윤현석
- Issue Date
- 2018
- Journal Title
- Scientific Reports
- ISSN
- 2045-2322
- Citation
- Scientific Reports vol. 8, no. 1
- Publisher
- Nature Publishing Group
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Interstitial cystitis (IC) is a chronic urinary tract disease that is characterized by unpleasant sensations, such as persistent pelvic pain, in the absence of infection or other identifiable causes. We previously performed comprehensive metabolomics profiling of urine samples from IC patients using nuclear magnetic resonance and gas-chromatography/mass spectrometry and found that urinary α-oxoglutarate (α-OG), was significantly elevated. α-OG, a tricarboxylic acid (TCA) cycle intermediate, reportedly functions to suppress the proliferation of immortalized normal human bladder epithelial cells. Here, we identified AT-rich interactive domain 1 A (ARID1A), a key chromatin remodeler, as being hypomethylated and upregulated by α-OG treatment. This was done through EPIC DNA methylation profiling and subsequent biochemical approaches, including quantitative RT-PCR and western blot analyses. Furthermore, we found that α-OG almost completely suppresses ten-eleven translocation (TET) activity, but does not affect DNA methyltransferase (DNMT) activity. Altogether, our studies reveal the potential role of α-OG in epigenetic remodeling through its effects on ARID1A and TET expression in the bladder. This may provide a new possible therapeutic strategy in treating IC. © 2018 The Author(s).
- DOI
- 10.1038/s41598-018-22771-2
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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