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Inhibition of Histone Deacetylase 10 Induces Thioredoxin-Interacting Protein and Causes Accumulation of Reactive Oxygen Species in SNU-620 Human Gastric Cancer Cells

Cited 44 time in Web of Science Cited 47 time in Scopus
Authors
Lee, Ju-Hee; Jeong, Eun-Goo; Choi, Moon-Chang; Kim, Sung-Hak; Song, Sang-Hyun; Bang, Yung-Jue; Kim, Tae-You; Park, Jinah; Park, Jung-Hyun
Issue Date
2010-08
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Citation
MOLECULES AND CELLS; Vol.30 2; 107-112
Keywords
histone deacetylase10human gastric cancer cellthioredoxin-interacting proteinthioredoxinreactive oxygen species
Abstract
Histone deacetylase (HDAC) 10, a novel class IIb histone deacetylase, is the most similar to HDAC6, since both contain a unique second catalytic domain. Unlike HDAC6, which is located in the cytoplasm, HDAC10 resides in both the nucleus and cytoplasm. The transcriptional targets of HDAC10 that are associated with HDAC10 gene regulation have not been identified. In the present study, we found that knockdown of HDAC10 significantly increased the mRNA expression levels of thioredoxin-interacting protein (TXNIP) in SNU-620 human gastric cancer cells; whereas inhibition of HDAC1, HDAC2, and HDAC6 did not affect TXNIP expression. TXNIP is the endogenous inhibitor of thioredoxin (TRX), which acts as a cellular antioxidant. Real-time PCR and immunoblot analysis confirmed that inhibition of HDAC10 induced TXNIP expression. Compared to class I only HDAC inhibitors, inhibitors targeting both class I and II upregulated TXNIP, indicating that TXNIP is regulated by class II HDACs such as HDAC10. We further verified that inhibition of HDAC10 induced release of cytochrome c and activated apoptotic signaling molecules through accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate that HDAC10 is involved in transcriptional downregulation of TXNIP, leading to altered ROS signaling in human gastric cancer cells. How TXNIP is preferentially regulated by HDAC10 needs further investigation.
ISSN
1016-8478
Language
English
URI
http://hdl.handle.net/10371/76469
DOI
https://doi.org/10.1007/s10059-010-0094-z
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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