Erythropoietin regulates the expression of dimeric form of acetylcholinesterase during differentiation of erythroblast

Autor: Ping Yao, Etta Y. L. Liu, Miranda L. Xu, Karl Wah Keung Tsim, Tina T. X. Dong, Wilson K.W. Luk, Kevin Qiyun Wu, Cathy W. C. Bi
Rok vydání: 2018
Předmět:
0301 basic medicine
Chromatin Immunoprecipitation
Time Factors
Erythroblasts
Morpholines
Gene Expression
Transfection
Biochemistry
Cell Line
Membrane Lipids
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Erythroblast
hemic and lymphatic diseases
Humans
GATA1 Transcription Factor
RNA
Messenger
Enzyme Inhibitors
Phosphorylation
Erythropoietin
Transcription factor
Protein kinase B
Regulation of gene expression
Dose-Response Relationship
Drug
Cell Differentiation
GATA1
Benzenaminium
4
4'-(3-oxo-1
5-pentanediyl)bis(N
N-dimethyl-N-2-propenyl-)
Dibromide
Acetylcholinesterase
Cell biology
030104 developmental biology
Gene Expression Regulation
chemistry
Chromones
Erythropoiesis
Proto-Oncogene Proteins c-akt
Chromatin immunoprecipitation
Signal Transduction
Zdroj: Journal of Neurochemistry. 146:390-402
ISSN: 0022-3042
DOI: 10.1111/jnc.14448
Popis: Acetylcholinesterase (AChE; EC 3.1.1.7) is known to hydrolyze acetylcholine at cholinergic synapses. In mammalian erythrocyte, AChE exists as a dimer (G2 ) and is proposed to play role in erythropoiesis. To reveal the regulation of AChE during differentiation of erythroblast, erythroblast-like cells (TF-1) were induced to differentiate by application of erythropoietin (EPO). The expression of AChE was increased in parallel to the stages of differentiation. Application of EPO in cultured TF-1 cells induced transcriptional activity of ACHE gene, as well as its protein product. This EPO-induced event was in parallel with erythrocytic proteins, for example, α- and β-globins. The EPO-induced AChE expression was mediated by phosphorylations of Akt and GATA-1; because the application of Akt kinase inhibitor blocked the gene activation. Erythroid transcription factor also known as GATA-1, a downstream transcription factor of EPO signaling, was proposed here to account for regulation of AChE in TF-1 cell. A binding sequence of GATA-1 was identified in ACHE gene promoter, which was further confirmed by chromatin immunoprecipitation (ChIP) assay. Over-expression of GATA-1 in TF-1 cultures induced AChE expression, as well as activity of ACHE promoter tagged with luciferase gene (pAChE-Luc). The deletion of GATA-1 sequence on the ACHE promoter, pAChEΔGATA-1 -Luc, reduced the promoter activity during erythroblastic differentiation. On the contrary, the knock-down of AChE in TF-1 cultures could lead to a reduction in EPO-induced expression of erythrocytic proteins. These findings indicated specific regulation of AChE during maturation of erythroblast, which provided an insight into elucidating possible mechanisms in regulating erythropoiesis.
Databáze: OpenAIRE
Externí odkaz: