Mitogenic effects of tetrahydrobiopterin in PC12 cells
(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted enzymatically to BH4 within cells, also increased...
Gespeichert in:
| Veröffentlicht in: | Molecular pharmacology 1996-01, Vol.49 (1), p.149-155 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 155 |
|---|---|
| container_issue | 1 |
| container_start_page | 149 |
| container_title | Molecular pharmacology |
| container_volume | 49 |
| creator | Anastasiadis, P Z States, J C Imerman, B A Louie, M C Kuhn, D M Levine, R A |
| description | (6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase
in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted
enzymatically to BH4 within cells, also increased PC12 cell proliferation and BH4 levels concomitantly. These sepiapterin
effects were mediated by BH4 as inhibition of sepiapterin conversion to BH4 by a sepiapterin reductase inhibitor, N-acetyl-serotonin,
blocked the increase in proliferation and the elevation of BH4 levels. 7,8-Dihydrobiopterin (BH2) also increased BH4 levels
and PC12 cell proliferation, both of which were reversed by methotrexate, which blocks the conversion of BH2 to BH4 by dihydrofolate
reductase. The BH4-induced increase in PC12 cell proliferation was not related to elevated catecholamine or nitric oxide synthesis
as inhibitors of tyrosine hydroxylase or nitric oxide synthase did not reduce the BH4 effect. BH4 and its precursors did not
alter intracellular cAMP levels, suggesting that this second messenger is not involved in the enhancement of PC12 cell proliferation
by BH4. Sepiapterin and BH4 also enhanced the proliferation of SV40-transformed human fibroblasts and rat C6 glioma cells,
indicating that the stimulatory effect of BH4 on cell proliferation is not restricted to PC12 cells. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_17023820</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17023820</sourcerecordid><originalsourceid>FETCH-LOGICAL-h267t-9d73c21f525ad100f5bbc20ce6d1709ef190110aab06c76e08ad72e6b46b5fd63</originalsourceid><addsrcrecordid>eNotj01LxDAYhIMo67r6E4Re9FZ4kzZpe5TFL1jRg4K3kI8320i7qUkW2X9vxYWBOczDMHNClpQzWgKl9JQsAZgo245_npOLlL4AaM1bWJBFy0XXACyJePE5bHHnTYHOocmpCK7ImKPqDzYG7cOUMfpdMettTVlhcBjSJTlzakh4dfQV-Xi4f18_lZvXx-f13absmWhy2dmmMow6zriyFMBxrQ0Dg8LSBjp0tJuXglIahGkEQqtsw1DoWmjurKhW5Pa_d4rhe48py9GnvwVqh2Gf5NzCqpbBDF4fwb0e0cop-lHFgzwenfOb_7z32_7HR5RTr-KoTBjC9iDrTlJJ6676BaTYXEI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17023820</pqid></control><display><type>article</type><title>Mitogenic effects of tetrahydrobiopterin in PC12 cells</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Anastasiadis, P Z ; States, J C ; Imerman, B A ; Louie, M C ; Kuhn, D M ; Levine, R A</creator><creatorcontrib>Anastasiadis, P Z ; States, J C ; Imerman, B A ; Louie, M C ; Kuhn, D M ; Levine, R A</creatorcontrib><description>(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase
in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted
enzymatically to BH4 within cells, also increased PC12 cell proliferation and BH4 levels concomitantly. These sepiapterin
effects were mediated by BH4 as inhibition of sepiapterin conversion to BH4 by a sepiapterin reductase inhibitor, N-acetyl-serotonin,
blocked the increase in proliferation and the elevation of BH4 levels. 7,8-Dihydrobiopterin (BH2) also increased BH4 levels
and PC12 cell proliferation, both of which were reversed by methotrexate, which blocks the conversion of BH2 to BH4 by dihydrofolate
reductase. The BH4-induced increase in PC12 cell proliferation was not related to elevated catecholamine or nitric oxide synthesis
as inhibitors of tyrosine hydroxylase or nitric oxide synthase did not reduce the BH4 effect. BH4 and its precursors did not
alter intracellular cAMP levels, suggesting that this second messenger is not involved in the enhancement of PC12 cell proliferation
by BH4. Sepiapterin and BH4 also enhanced the proliferation of SV40-transformed human fibroblasts and rat C6 glioma cells,
indicating that the stimulatory effect of BH4 on cell proliferation is not restricted to PC12 cells.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>PMID: 8569700</identifier><language>eng</language><publisher>United States: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Animals ; Biopterins - analogs & derivatives ; Biopterins - pharmacology ; Cell Division - drug effects ; Cell Line, Transformed ; Cyclic AMP - biosynthesis ; Cyclic AMP - metabolism ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Glioma - pathology ; Humans ; Mitogens - pharmacology ; PC12 Cells ; Rats</subject><ispartof>Molecular pharmacology, 1996-01, Vol.49 (1), p.149-155</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8569700$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anastasiadis, P Z</creatorcontrib><creatorcontrib>States, J C</creatorcontrib><creatorcontrib>Imerman, B A</creatorcontrib><creatorcontrib>Louie, M C</creatorcontrib><creatorcontrib>Kuhn, D M</creatorcontrib><creatorcontrib>Levine, R A</creatorcontrib><title>Mitogenic effects of tetrahydrobiopterin in PC12 cells</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase
in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted
enzymatically to BH4 within cells, also increased PC12 cell proliferation and BH4 levels concomitantly. These sepiapterin
effects were mediated by BH4 as inhibition of sepiapterin conversion to BH4 by a sepiapterin reductase inhibitor, N-acetyl-serotonin,
blocked the increase in proliferation and the elevation of BH4 levels. 7,8-Dihydrobiopterin (BH2) also increased BH4 levels
and PC12 cell proliferation, both of which were reversed by methotrexate, which blocks the conversion of BH2 to BH4 by dihydrofolate
reductase. The BH4-induced increase in PC12 cell proliferation was not related to elevated catecholamine or nitric oxide synthesis
as inhibitors of tyrosine hydroxylase or nitric oxide synthase did not reduce the BH4 effect. BH4 and its precursors did not
alter intracellular cAMP levels, suggesting that this second messenger is not involved in the enhancement of PC12 cell proliferation
by BH4. Sepiapterin and BH4 also enhanced the proliferation of SV40-transformed human fibroblasts and rat C6 glioma cells,
indicating that the stimulatory effect of BH4 on cell proliferation is not restricted to PC12 cells.</description><subject>Animals</subject><subject>Biopterins - analogs & derivatives</subject><subject>Biopterins - pharmacology</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Transformed</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Cyclic AMP - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Mitogens - pharmacology</subject><subject>PC12 Cells</subject><subject>Rats</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNotj01LxDAYhIMo67r6E4Re9FZ4kzZpe5TFL1jRg4K3kI8320i7qUkW2X9vxYWBOczDMHNClpQzWgKl9JQsAZgo245_npOLlL4AaM1bWJBFy0XXACyJePE5bHHnTYHOocmpCK7ImKPqDzYG7cOUMfpdMettTVlhcBjSJTlzakh4dfQV-Xi4f18_lZvXx-f13absmWhy2dmmMow6zriyFMBxrQ0Dg8LSBjp0tJuXglIahGkEQqtsw1DoWmjurKhW5Pa_d4rhe48py9GnvwVqh2Gf5NzCqpbBDF4fwb0e0cop-lHFgzwenfOb_7z32_7HR5RTr-KoTBjC9iDrTlJJ6676BaTYXEI</recordid><startdate>19960101</startdate><enddate>19960101</enddate><creator>Anastasiadis, P Z</creator><creator>States, J C</creator><creator>Imerman, B A</creator><creator>Louie, M C</creator><creator>Kuhn, D M</creator><creator>Levine, R A</creator><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>19960101</creationdate><title>Mitogenic effects of tetrahydrobiopterin in PC12 cells</title><author>Anastasiadis, P Z ; States, J C ; Imerman, B A ; Louie, M C ; Kuhn, D M ; Levine, R A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-9d73c21f525ad100f5bbc20ce6d1709ef190110aab06c76e08ad72e6b46b5fd63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Biopterins - analogs & derivatives</topic><topic>Biopterins - pharmacology</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Transformed</topic><topic>Cyclic AMP - biosynthesis</topic><topic>Cyclic AMP - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Glioma - pathology</topic><topic>Humans</topic><topic>Mitogens - pharmacology</topic><topic>PC12 Cells</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anastasiadis, P Z</creatorcontrib><creatorcontrib>States, J C</creatorcontrib><creatorcontrib>Imerman, B A</creatorcontrib><creatorcontrib>Louie, M C</creatorcontrib><creatorcontrib>Kuhn, D M</creatorcontrib><creatorcontrib>Levine, R A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anastasiadis, P Z</au><au>States, J C</au><au>Imerman, B A</au><au>Louie, M C</au><au>Kuhn, D M</au><au>Levine, R A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitogenic effects of tetrahydrobiopterin in PC12 cells</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1996-01-01</date><risdate>1996</risdate><volume>49</volume><issue>1</issue><spage>149</spage><epage>155</epage><pages>149-155</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><abstract>(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase
in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted
enzymatically to BH4 within cells, also increased PC12 cell proliferation and BH4 levels concomitantly. These sepiapterin
effects were mediated by BH4 as inhibition of sepiapterin conversion to BH4 by a sepiapterin reductase inhibitor, N-acetyl-serotonin,
blocked the increase in proliferation and the elevation of BH4 levels. 7,8-Dihydrobiopterin (BH2) also increased BH4 levels
and PC12 cell proliferation, both of which were reversed by methotrexate, which blocks the conversion of BH2 to BH4 by dihydrofolate
reductase. The BH4-induced increase in PC12 cell proliferation was not related to elevated catecholamine or nitric oxide synthesis
as inhibitors of tyrosine hydroxylase or nitric oxide synthase did not reduce the BH4 effect. BH4 and its precursors did not
alter intracellular cAMP levels, suggesting that this second messenger is not involved in the enhancement of PC12 cell proliferation
by BH4. Sepiapterin and BH4 also enhanced the proliferation of SV40-transformed human fibroblasts and rat C6 glioma cells,
indicating that the stimulatory effect of BH4 on cell proliferation is not restricted to PC12 cells.</abstract><cop>United States</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>8569700</pmid><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0026-895X |
| ispartof | Molecular pharmacology, 1996-01, Vol.49 (1), p.149-155 |
| issn | 0026-895X 1521-0111 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17023820 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biopterins - analogs & derivatives Biopterins - pharmacology Cell Division - drug effects Cell Line, Transformed Cyclic AMP - biosynthesis Cyclic AMP - metabolism Fibroblasts - cytology Fibroblasts - drug effects Glioma - pathology Humans Mitogens - pharmacology PC12 Cells Rats |
| title | Mitogenic effects of tetrahydrobiopterin in PC12 cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T23%3A45%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitogenic%20effects%20of%20tetrahydrobiopterin%20in%20PC12%20cells&rft.jtitle=Molecular%20pharmacology&rft.au=Anastasiadis,%20P%20Z&rft.date=1996-01-01&rft.volume=49&rft.issue=1&rft.spage=149&rft.epage=155&rft.pages=149-155&rft.issn=0026-895X&rft.eissn=1521-0111&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E17023820%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17023820&rft_id=info:pmid/8569700&rfr_iscdi=true |