Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

Biochemical and Biophysical Research Communications
Hye-Ryeong JoHyeon Son

Abstract

Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

References

Apr 1, 1996·The European Journal of Neuroscience·H H MartiM Gassmann
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·J LuE N Olson
Dec 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·T A McKinseyE N Olson
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·A H KosselT Bonhoeffer
Jul 26, 2002·Journal of the American Society of Nephrology : JASN·Zhiyuan YuBruce C Kone
Mar 19, 2003·Journal of Neurochemistry·Sangeeta ChawlaHilmar Bading
Feb 26, 2005·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Stefanie SchmetsdorfThomas Arendt
Apr 25, 2006·Biological Psychiatry·Ronald S Duman, Lisa M Monteggia
May 31, 2011·Best Practice & Research. Clinical Anaesthesiology·Derya SarginHannelore Ehrenreich
Jan 17, 2012·Neuron·Makoto TaniguchiChristopher W Cowan
Feb 24, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jahan Salma, John C McDermott
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hyeon SonRonald S Duman
Nov 12, 2013·Cell·Yongcheol ChoValeria Cavalli
Mar 13, 2014·Biochemical and Biophysical Research Communications·Miyeon ChoiHyeon Son
Jul 30, 2014·Frontiers in Genetics·Fabio Coppedè
Dec 9, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Karin Meier, Alexander Brehm

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.