PMID- 32542592
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20220724
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 57
IP  - 8
DP  - 2020 Aug
TI  - Epigenetic Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain 
      Barrier.
PG  - 3526-3539
LID - 10.1007/s12035-020-01953-y [doi]
AB  - Ferroportin plays an essential role for iron transport through the blood-brain 
      barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). To 
      maintain the integrity of the BBB, the BCECs gain support from pericytes and 
      astrocytes, which together with neurons form the neurovascular unit (NVU). The 
      objectives of the present study were to investigate ferroportin expression in 
      primary cells of the NVU and to determine if ferroportin mRNA (Fpn) expression is 
      epigenetically regulated. Primary rat BCECs, pericytes, astrocytes, and neurons 
      all expressed ferroportin mRNA at varying levels, with BCECs exhibiting the 
      highest expression of Fpn, peaking when co-cultured but examined separately from 
      astrocytes. Conversely, Fpn expression was lowest in isolated astrocytes, which 
      correlated with high DNA methylation in their Slc40a1 promoter. To provide 
      further evidence for epigenetic regulation, mono-cultured BCECs, pericytes, and 
      astrocytes were treated with the histone deacetylase inhibitors valproic acid 
      (VPA) and sodium butyrate (SB), which significantly increased Fpn and ferroportin 
      protein in BCECs and pericytes. Furthermore, (59)Fe export from BCECs was 
      elevated after treatment with VPA. In conclusion, we present first time evidence 
      stating that Fpn expression is epigenetically regulated in BCECs, which may have 
      implications for pharmacological induction of iron transport through the BBB.
FAU - Helgudottir, Steinunn Sara
AU  - Helgudottir SS
AD  - Neurobiology Research and Drug Delivery (NRD) Department of Health Science and 
      Technology, Aalborg University, Fr. Bajers Vej 3B, 9220, Aalborg, Denmark.
FAU - Routhe, Lisa J
AU  - Routhe LJ
AD  - Neurobiology Research and Drug Delivery (NRD) Department of Health Science and 
      Technology, Aalborg University, Fr. Bajers Vej 3B, 9220, Aalborg, Denmark.
FAU - Burkhart, Annette
AU  - Burkhart A
AD  - Neurobiology Research and Drug Delivery (NRD) Department of Health Science and 
      Technology, Aalborg University, Fr. Bajers Vej 3B, 9220, Aalborg, Denmark.
FAU - Jonsson, Katrine
AU  - Jonsson K
AD  - Department of Health Technology, Center for Nanomedicine and Theranostics, 
      Technical University of Denmark, Copenhagen, Denmark.
FAU - Pedersen, Inge S
AU  - Pedersen IS
AD  - Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
AD  - Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, 
      Denmark.
FAU - Lichota, Jacek
AU  - Lichota J
AD  - Laboratory of Molecular Pharmacology, Department of Health Science and 
      Technology, Aalborg University, Fr. Bajers Vej 7E, 9220, Aalborg, Denmark. 
      jlichota@hst.aau.dk.
FAU - Moos, Torben
AU  - Moos T
AUID- ORCID: 0000-0001-9989-0207
AD  - Neurobiology Research and Drug Delivery (NRD) Department of Health Science and 
      Technology, Aalborg University, Fr. Bajers Vej 3B, 9220, Aalborg, Denmark. 
      tmoos@hst.aau.dk.
LA  - eng
GR  - R155-2013-14113/Lundbeckfonden/
GR  - A35923/Scleroseforeningen/
PT  - Journal Article
DEP - 20200615
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Biological Transport/physiology
MH  - Blood-Brain Barrier/*metabolism
MH  - Brain/metabolism
MH  - Capillaries/metabolism
MH  - Coculture Techniques/methods
MH  - Endothelial Cells/*metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Epigenesis, Genetic/physiology
MH  - Neurons/*metabolism
MH  - Pericytes/*metabolism
MH  - Rats
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - DNA methylation
OT  - Epigenetics
OT  - Sodium butyrate
OT  - Valproic acid
EDAT- 2020/06/17 06:00
MHDA- 2021/06/08 06:00
CRDT- 2020/06/17 06:00
PHST- 2019/12/08 00:00 [received]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/06/17 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2020/06/17 06:00 [entrez]
AID - 10.1007/s12035-020-01953-y [pii]
AID - 10.1007/s12035-020-01953-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2020 Aug;57(8):3526-3539. doi: 10.1007/s12035-020-01953-y. Epub 
      2020 Jun 15.