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Author Jo, Hye-Ryeong ♦ Kim, Yong-Seok ♦ Son, Hyeon
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ BRAIN ♦ CALCIUM ♦ CALMODULIN ♦ ERYTHROPOIETIN ♦ GENES ♦ HAZARDS ♦ HISTONES ♦ NERVE CELLS ♦ PHOSPHORYLATION ♦ RATS
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.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-01-29
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 470
Issue Number 1


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