Epigenetic Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain Barrier
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 u...
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| Veröffentlicht in: | Molecular neurobiology 2020-08, Vol.57 (8), p.3526-3539 |
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| creator | Helgudottir, Steinunn Sara Routhe, Lisa J. Burkhart, Annette Jønsson, Katrine Pedersen, Inge S. Lichota, Jacek Moos, Torben |
| description | 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. |
| doi_str_mv | 10.1007/s12035-020-01953-y |
| format | Article |
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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.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-020-01953-y</identifier><identifier>PMID: 32542592</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Astrocytes ; Biomedical and Life Sciences ; Biomedicine ; Blood-brain barrier ; Cell Biology ; DNA methylation ; Endothelial cells ; Epigenetics ; Gene expression ; Histone deacetylase ; Iron ; Life Sciences & Biomedicine ; mRNA ; Neurobiology ; Neurology ; Neurosciences ; Neurosciences & Neurology ; Original Article ; Pericytes ; Science & Technology ; Sodium butyrate ; Valproic acid</subject><ispartof>Molecular neurobiology, 2020-08, Vol.57 (8), p.3526-3539</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>7</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000540406100001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c352t-aba248da8d7b2ebf50e165df6ddc3e96092f4d8faf2070c4102abce60ada9b423</citedby><cites>FETCH-LOGICAL-c352t-aba248da8d7b2ebf50e165df6ddc3e96092f4d8faf2070c4102abce60ada9b423</cites><orcidid>0000-0001-9989-0207 ; 0000-0002-9902-8040 ; 0000-0003-3658-5859 ; 0000-0002-9943-5201 ; 0000-0003-2452-7504</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-020-01953-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-020-01953-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,28257,41497,42566,51328</link.rule.ids></links><search><creatorcontrib>Helgudottir, Steinunn Sara</creatorcontrib><creatorcontrib>Routhe, Lisa J.</creatorcontrib><creatorcontrib>Burkhart, Annette</creatorcontrib><creatorcontrib>Jønsson, Katrine</creatorcontrib><creatorcontrib>Pedersen, Inge S.</creatorcontrib><creatorcontrib>Lichota, Jacek</creatorcontrib><creatorcontrib>Moos, Torben</creatorcontrib><title>Epigenetic Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain Barrier</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>MOL NEUROBIOL</addtitle><description>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.</description><subject>Astrocytes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-brain barrier</subject><subject>Cell Biology</subject><subject>DNA methylation</subject><subject>Endothelial cells</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Histone deacetylase</subject><subject>Iron</subject><subject>Life Sciences & Biomedicine</subject><subject>mRNA</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurosciences & Neurology</subject><subject>Original Article</subject><subject>Pericytes</subject><subject>Science & Technology</subject><subject>Sodium butyrate</subject><subject>Valproic 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Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain Barrier</title><author>Helgudottir, Steinunn Sara ; Routhe, Lisa J. ; Burkhart, Annette ; Jønsson, Katrine ; Pedersen, Inge S. ; Lichota, Jacek ; Moos, Torben</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-aba248da8d7b2ebf50e165df6ddc3e96092f4d8faf2070c4102abce60ada9b423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Astrocytes</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood-brain barrier</topic><topic>Cell Biology</topic><topic>DNA methylation</topic><topic>Endothelial cells</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Histone deacetylase</topic><topic>Iron</topic><topic>Life Sciences & Biomedicine</topic><topic>mRNA</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Neurosciences & 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Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Helgudottir, Steinunn Sara</au><au>Routhe, Lisa J.</au><au>Burkhart, Annette</au><au>Jønsson, Katrine</au><au>Pedersen, Inge S.</au><au>Lichota, Jacek</au><au>Moos, Torben</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain Barrier</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><stitle>MOL NEUROBIOL</stitle><date>2020-08-01</date><risdate>2020</risdate><volume>57</volume><issue>8</issue><spage>3526</spage><epage>3539</epage><pages>3526-3539</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32542592</pmid><doi>10.1007/s12035-020-01953-y</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-9989-0207</orcidid><orcidid>https://orcid.org/0000-0002-9902-8040</orcidid><orcidid>https://orcid.org/0000-0003-3658-5859</orcidid><orcidid>https://orcid.org/0000-0002-9943-5201</orcidid><orcidid>https://orcid.org/0000-0003-2452-7504</orcidid></addata></record> |
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| subjects | Astrocytes Biomedical and Life Sciences Biomedicine Blood-brain barrier Cell Biology DNA methylation Endothelial cells Epigenetics Gene expression Histone deacetylase Iron Life Sciences & Biomedicine mRNA Neurobiology Neurology Neurosciences Neurosciences & Neurology Original Article Pericytes Science & Technology Sodium butyrate Valproic acid |
| title | Epigenetic Regulation of Ferroportin in Primary Cultures of the Rat Blood-Brain Barrier |
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