EZH2-inhibitor DZNep enhances apoptosis of renal tubular epithelial cells in presence and absence of cisplatin

Cell Division
Si-Qi ChenHong-Xin Niu

Abstract

The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated. NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay. The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cell...Continue Reading

References

Mar 15, 2002·Current Opinion in Genetics & Development·Jeffrey A Simon, John W Tamkun
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Dec 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ingeborg M BachmannLars A Akslen
Oct 25, 2006·Nature Reviews. Cancer·Anke Sparmann, Maarten van Lohuizen
May 31, 2007·Cell Cycle·Kotb AbdelmohsenMyriam Gorospe
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Apr 30, 2010·The Journal of Biological Chemistry·Takeshi KaizukaNoboru Mizushima
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Jun 14, 2014·Journal of the American Society of Nephrology : JASN·Andreas LinkermannZheng Dong
Jul 30, 2014·Journal of Endodontics·Tianqian HuiLing Ye
Nov 14, 2014·Journal of the American Society of Nephrology : JASN·Jun AiFan Fan Hou
Nov 5, 2015·Journal of the American Society of Nephrology : JASN·Ferhan S SiddiqiAndrew Advani
Dec 25, 2015·Journal of the American Society of Nephrology : JASN·Xiaoxu ZhouShougang Zhuang
Sep 17, 2017·Bioorganic & Medicinal Chemistry Letters·Jihye LeeAlan Lichtenstein

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
immunoprecipitation
ChIP
PCR

Software Mentioned

SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.