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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
윤하나윤현석
SCOPUS Author ID
윤하나scopus; 윤현석scopus
Issue Date
2018
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 8, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
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
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의료원 > 의료원 > Journal papers
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