Oxygen Tension Modulates Neurite Outgrowth in PC12 Cells Through A Mechanism Involving HIF and VEGF
Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), y...
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| Veröffentlicht in: | Journal of molecular neuroscience 2010-03, Vol.40 (3), p.360-366 |
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| creator | Genetos, Damian C. Cheung, Whitney K. Decaris, Martin L. Leach, J. Kent |
| description | Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1α stabilization. The hypoxic target gene
Vegf
was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment
via
VEGF function, and suggest promising approaches for future applications in neural repair. |
| doi_str_mv | 10.1007/s12031-009-9326-0 |
| format | Article |
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Vegf
was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment
via
VEGF function, and suggest promising approaches for future applications in neural repair.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/s12031-009-9326-0</identifier><identifier>PMID: 20107925</identifier><language>eng</language><publisher>New York: Humana Press Inc</publisher><subject>Animals ; Antibodies ; Apoptosis ; Axon guidance ; Axonogenesis ; Biomedical and Life Sciences ; Biomedicine ; Bone marrow ; Carbon dioxide ; Cell Biology ; Cell culture ; Cell Differentiation - physiology ; Differentiation ; Humans ; Hypoxia ; Hypoxia - metabolism ; Hypoxia-inducible factor 1 alpha ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Injuries ; Microenvironments ; Morphology ; Nervous system ; Neurites - metabolism ; Neurites - ultrastructure ; Neurochemistry ; Neurology ; Neurosciences ; Neurotrophic factors ; Oxygen - metabolism ; Oxygen tension ; PC12 Cells - cytology ; PC12 Cells - metabolism ; Pheochromocytoma cells ; Physiology ; Proteomics ; Rats ; Signal Transduction - physiology ; Stem cells ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factors - metabolism</subject><ispartof>Journal of molecular neuroscience, 2010-03, Vol.40 (3), p.360-366</ispartof><rights>The Author(s) 2010</rights><rights>Springer Science+Business Media, LLC 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-d5436212106dab0fcb1115be5ea2becf25c28fb87be65af126d337d7aea327473</citedby><cites>FETCH-LOGICAL-c500t-d5436212106dab0fcb1115be5ea2becf25c28fb87be65af126d337d7aea327473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12031-009-9326-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12031-009-9326-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20107925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Genetos, Damian C.</creatorcontrib><creatorcontrib>Cheung, Whitney K.</creatorcontrib><creatorcontrib>Decaris, Martin L.</creatorcontrib><creatorcontrib>Leach, J. Kent</creatorcontrib><title>Oxygen Tension Modulates Neurite Outgrowth in PC12 Cells Through A Mechanism Involving HIF and VEGF</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><addtitle>J Mol Neurosci</addtitle><description>Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1α stabilization. The hypoxic target gene
Vegf
was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment
via
VEGF function, and suggest promising approaches for future applications in neural repair.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Axon guidance</subject><subject>Axonogenesis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone marrow</subject><subject>Carbon dioxide</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell Differentiation - physiology</subject><subject>Differentiation</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia - metabolism</subject><subject>Hypoxia-inducible factor 1 alpha</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Injuries</subject><subject>Microenvironments</subject><subject>Morphology</subject><subject>Nervous system</subject><subject>Neurites - metabolism</subject><subject>Neurites - ultrastructure</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurotrophic factors</subject><subject>Oxygen - metabolism</subject><subject>Oxygen tension</subject><subject>PC12 Cells - cytology</subject><subject>PC12 Cells - metabolism</subject><subject>Pheochromocytoma cells</subject><subject>Physiology</subject><subject>Proteomics</subject><subject>Rats</subject><subject>Signal Transduction - physiology</subject><subject>Stem cells</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factors - metabolism</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU1v1DAQhi0EokvhB3BBFpeeAjP22k4uSNWq267UshwWrpaTTLKpsnaxk4X-e7LaUj4kxMmHeebxzLyMvUZ4hwDmfUIBEjOAIiuk0Bk8YTNUqsgQtX7KZpAXKst1oU_Yi5RuAQTOMX_OTgQgmEKoGavW3-9b8nxDPnXB85tQj70bKPGPNMZuIL4ehzaGb8OWd55_WqDgC-r7xDfbGMZ2y8_5DVVb57u04yu_D_2-8y2_Wi258zX_cnG5fMmeNa5P9OrhPWWflxebxVV2vb5cLc6vs0oBDFmt5lILFAi6diU0VYmIqiRFTpRUNUJVIm_K3JSklWtQ6FpKUxtHTgozN_KUfTh678ZyR3VFfoiut3ex27l4b4Pr7J8V321tG_ZW5EJJ1JPg7EEQw9eR0mB3XaqmbZ2nMCZbqLnWqKD4L2mknGClD0O9_Yu8DWP00x1sblAZpfKDDo9QFUNKkZrHoRHsIWp7jNpOUdtD1Bamnje_b_vY8TPbCRBHIE0l31L89fO_rT8A70yzag</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Genetos, Damian C.</creator><creator>Cheung, Whitney K.</creator><creator>Decaris, Martin L.</creator><creator>Leach, J. 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Kent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxygen Tension Modulates Neurite Outgrowth in PC12 Cells Through A Mechanism Involving HIF and VEGF</atitle><jtitle>Journal of molecular neuroscience</jtitle><stitle>J Mol Neurosci</stitle><addtitle>J Mol Neurosci</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>40</volume><issue>3</issue><spage>360</spage><epage>366</epage><pages>360-366</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>Cell-based approaches are a promising therapeutic strategy for treating injuries to the nervous system, but the optimal means to promote neurite extension and direct cellular behavior are unclear. Previous studies have examined the behavior of neural-like cells in ambient air (21% oxygen tension), yet these conditions are not representative of the physiological oxygen microenvironment of neural tissues. We hypothesized that neuronal differentiation of a model neural cell line (PC12) could be controlled by modulating local oxygen tension. Compared to ambient conditions, PC12 cells cultured in reduced oxygen exhibited significant increases in neurite extension and total neurite length, with 4% oxygen yielding the highest levels of both indicators. We confirmed neurite extension was mediated through oxygen-responsive mechanisms using small molecules that promote or inhibit HIF-1α stabilization. The hypoxic target gene
Vegf
was implicated as a neurotrophic factor, as neurite formation at 21% oxygen was mimicked with exogenous VEGF, and a VEGF-neutralizing antibody attenuated neurite formation under reduced oxygen conditions. These findings demonstrate that behavior of neural-like cells is driven by the oxygen microenvironment
via
VEGF function, and suggest promising approaches for future applications in neural repair.</abstract><cop>New York</cop><pub>Humana Press Inc</pub><pmid>20107925</pmid><doi>10.1007/s12031-009-9326-0</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies Apoptosis Axon guidance Axonogenesis Biomedical and Life Sciences Biomedicine Bone marrow Carbon dioxide Cell Biology Cell culture Cell Differentiation - physiology Differentiation Humans Hypoxia Hypoxia - metabolism Hypoxia-inducible factor 1 alpha Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Injuries Microenvironments Morphology Nervous system Neurites - metabolism Neurites - ultrastructure Neurochemistry Neurology Neurosciences Neurotrophic factors Oxygen - metabolism Oxygen tension PC12 Cells - cytology PC12 Cells - metabolism Pheochromocytoma cells Physiology Proteomics Rats Signal Transduction - physiology Stem cells Vascular endothelial growth factor Vascular Endothelial Growth Factors - metabolism |
| title | Oxygen Tension Modulates Neurite Outgrowth in PC12 Cells Through A Mechanism Involving HIF and VEGF |
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