Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress
Vascular endothelial growth factor (VEGF) plays an important role in initiation of the angiogenesis that leads to proliferative retinopathy. Several environmental conditions and chemical agents that influence the expression of VEGF can also cause endoplasmic reticulum (ER) stress. The hypothesis for...
Gespeichert in:
| Veröffentlicht in: | Investigative ophthalmology & visual science 2002-08, Vol.43 (8), p.2791-2798 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2798 |
|---|---|
| container_issue | 8 |
| container_start_page | 2791 |
| container_title | Investigative ophthalmology & visual science |
| container_volume | 43 |
| creator | Abcouwer, Steve F Marjon, Philip L Loper, Robyn K Vander Jagt, David L |
| description | Vascular endothelial growth factor (VEGF) plays an important role in initiation of the angiogenesis that leads to proliferative retinopathy. Several environmental conditions and chemical agents that influence the expression of VEGF can also cause endoplasmic reticulum (ER) stress. The hypothesis for the current study was that expression of VEGF is responsive to conditions that cause ER stress, including amino acid deprivation.
Confluent cultures of a human retinal pigmented epithelial cell line (ARPE-19) were deprived of amino acids or treated with chemical inducers of ER stress. Treatment with cobalt was used to mimic hypoxia-induced expression of VEGF. Northern blot analysis was used to measure intracellular VEGF mRNA, and ELISA was used to measure secreted VEGF protein. Glucose-regulated protein 78 (GRP78) mRNA levels were compared with those of VEGF. Glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA was used as a control.
Conditions and chemical agents known to activate ER stress response (ERSR) pathways also induced the expression of VEGF. Deprivation of amino acids in the culture medium increased VEGF mRNA expression by 1.3- to 6-fold. Glucose deprivation or treatment of ARPE-19 cells with tunicamycin, brefeldin A, the calcium ionophore A23187, or thapsigargin increased the expression of VEGF mRNA in these cells by 8- to 10-fold. Expression of GRP78 mRNA was well correlated with that of VEGF mRNA under all conditions. These treatments also increased the secretion of VEGF protein by up to twofold. The increase in VEGF mRNA level in response to glutamine deprivation was rapid (greater than 10-fold) and was observed in a physiologically relevant range of glutamine concentrations. The half-life of VEGF mRNA was increased 2.5-fold by glutamine starvation.
These results indicate that VEGF is an ER stress-responsive gene and suggest that cells can respond to nutrient deprivation by increasing VEGF expression through both transcriptional and posttranscriptional mechanisms. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_71949150</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71949150</sourcerecordid><originalsourceid>FETCH-LOGICAL-h268t-d9fbc9f161a8364792625e6b35824ea37e3ec271e665c76d52e9ae23387edfae3</originalsourceid><addsrcrecordid>eNpFkE1Lw0AQhoMotlb_guxFb4H93uRYalsLBaF-XJfNZmJXNh9mE6P_3hQrvcwc5plnmPcsmhIhaCxUws6jKSZcxphjPomuQvjAmBJC8WU0IZRwJYmaRtkOQlNXAVBdoLfleoWW300LIbi6Ql2N5qWrxmpdjh6gad2X6Q4TU-VoU-W9hTYcNpdVXjfehNJZtIPO2d73JXruDqbr6KIwPsDNsc-i19XyZfEYb5_Wm8V8G--pTLo4T4vMpgWRxCRMcpVSSQXIjImEcjBMAQNLFQEphVUyFxRSA5SxREFeGGCz6P7P27T1Zw-h06ULFrw3FdR90IqkPCUCj-DtEeyzEnI9vlWa9kf_pzICd0fABGt80ZrKunDiWIITLOXp4t697wfXgg6l8X7UEj0MA2c60VSlhP0CA4x5OQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71949150</pqid></control><display><type>article</type><title>Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Abcouwer, Steve F ; Marjon, Philip L ; Loper, Robyn K ; Vander Jagt, David L</creator><creatorcontrib>Abcouwer, Steve F ; Marjon, Philip L ; Loper, Robyn K ; Vander Jagt, David L</creatorcontrib><description>Vascular endothelial growth factor (VEGF) plays an important role in initiation of the angiogenesis that leads to proliferative retinopathy. Several environmental conditions and chemical agents that influence the expression of VEGF can also cause endoplasmic reticulum (ER) stress. The hypothesis for the current study was that expression of VEGF is responsive to conditions that cause ER stress, including amino acid deprivation.
Confluent cultures of a human retinal pigmented epithelial cell line (ARPE-19) were deprived of amino acids or treated with chemical inducers of ER stress. Treatment with cobalt was used to mimic hypoxia-induced expression of VEGF. Northern blot analysis was used to measure intracellular VEGF mRNA, and ELISA was used to measure secreted VEGF protein. Glucose-regulated protein 78 (GRP78) mRNA levels were compared with those of VEGF. Glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA was used as a control.
Conditions and chemical agents known to activate ER stress response (ERSR) pathways also induced the expression of VEGF. Deprivation of amino acids in the culture medium increased VEGF mRNA expression by 1.3- to 6-fold. Glucose deprivation or treatment of ARPE-19 cells with tunicamycin, brefeldin A, the calcium ionophore A23187, or thapsigargin increased the expression of VEGF mRNA in these cells by 8- to 10-fold. Expression of GRP78 mRNA was well correlated with that of VEGF mRNA under all conditions. These treatments also increased the secretion of VEGF protein by up to twofold. The increase in VEGF mRNA level in response to glutamine deprivation was rapid (greater than 10-fold) and was observed in a physiologically relevant range of glutamine concentrations. The half-life of VEGF mRNA was increased 2.5-fold by glutamine starvation.
These results indicate that VEGF is an ER stress-responsive gene and suggest that cells can respond to nutrient deprivation by increasing VEGF expression through both transcriptional and posttranscriptional mechanisms.</description><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>PMID: 12147617</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Amino Acids - deficiency ; Biological and medical sciences ; Blotting, Northern ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Hypoxia - physiology ; Cells, Cultured ; Endoplasmic Reticulum - physiology ; Endothelial Growth Factors - genetics ; Endothelial Growth Factors - metabolism ; Enzyme-Linked Immunosorbent Assay ; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics ; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism ; Heat-Shock Proteins ; Humans ; Lymphokines - genetics ; Lymphokines - metabolism ; Medical sciences ; Molecular Chaperones - genetics ; Molecular Chaperones - metabolism ; Ophthalmology ; Pigment Epithelium of Eye - metabolism ; Retinopathies ; RNA, Messenger - metabolism ; Stress, Physiological - metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Investigative ophthalmology & visual science, 2002-08, Vol.43 (8), p.2791-2798</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13808066$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12147617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abcouwer, Steve F</creatorcontrib><creatorcontrib>Marjon, Philip L</creatorcontrib><creatorcontrib>Loper, Robyn K</creatorcontrib><creatorcontrib>Vander Jagt, David L</creatorcontrib><title>Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Vascular endothelial growth factor (VEGF) plays an important role in initiation of the angiogenesis that leads to proliferative retinopathy. Several environmental conditions and chemical agents that influence the expression of VEGF can also cause endoplasmic reticulum (ER) stress. The hypothesis for the current study was that expression of VEGF is responsive to conditions that cause ER stress, including amino acid deprivation.
Confluent cultures of a human retinal pigmented epithelial cell line (ARPE-19) were deprived of amino acids or treated with chemical inducers of ER stress. Treatment with cobalt was used to mimic hypoxia-induced expression of VEGF. Northern blot analysis was used to measure intracellular VEGF mRNA, and ELISA was used to measure secreted VEGF protein. Glucose-regulated protein 78 (GRP78) mRNA levels were compared with those of VEGF. Glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA was used as a control.
Conditions and chemical agents known to activate ER stress response (ERSR) pathways also induced the expression of VEGF. Deprivation of amino acids in the culture medium increased VEGF mRNA expression by 1.3- to 6-fold. Glucose deprivation or treatment of ARPE-19 cells with tunicamycin, brefeldin A, the calcium ionophore A23187, or thapsigargin increased the expression of VEGF mRNA in these cells by 8- to 10-fold. Expression of GRP78 mRNA was well correlated with that of VEGF mRNA under all conditions. These treatments also increased the secretion of VEGF protein by up to twofold. The increase in VEGF mRNA level in response to glutamine deprivation was rapid (greater than 10-fold) and was observed in a physiologically relevant range of glutamine concentrations. The half-life of VEGF mRNA was increased 2.5-fold by glutamine starvation.
These results indicate that VEGF is an ER stress-responsive gene and suggest that cells can respond to nutrient deprivation by increasing VEGF expression through both transcriptional and posttranscriptional mechanisms.</description><subject>Amino Acids - deficiency</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Hypoxia - physiology</subject><subject>Cells, Cultured</subject><subject>Endoplasmic Reticulum - physiology</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Endothelial Growth Factors - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Glyceraldehyde-3-Phosphate Dehydrogenases - genetics</subject><subject>Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism</subject><subject>Heat-Shock Proteins</subject><subject>Humans</subject><subject>Lymphokines - genetics</subject><subject>Lymphokines - metabolism</subject><subject>Medical sciences</subject><subject>Molecular Chaperones - genetics</subject><subject>Molecular Chaperones - metabolism</subject><subject>Ophthalmology</subject><subject>Pigment Epithelium of Eye - metabolism</subject><subject>Retinopathies</subject><subject>RNA, Messenger - metabolism</subject><subject>Stress, Physiological - metabolism</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1Lw0AQhoMotlb_guxFb4H93uRYalsLBaF-XJfNZmJXNh9mE6P_3hQrvcwc5plnmPcsmhIhaCxUws6jKSZcxphjPomuQvjAmBJC8WU0IZRwJYmaRtkOQlNXAVBdoLfleoWW300LIbi6Ql2N5qWrxmpdjh6gad2X6Q4TU-VoU-W9hTYcNpdVXjfehNJZtIPO2d73JXruDqbr6KIwPsDNsc-i19XyZfEYb5_Wm8V8G--pTLo4T4vMpgWRxCRMcpVSSQXIjImEcjBMAQNLFQEphVUyFxRSA5SxREFeGGCz6P7P27T1Zw-h06ULFrw3FdR90IqkPCUCj-DtEeyzEnI9vlWa9kf_pzICd0fABGt80ZrKunDiWIITLOXp4t697wfXgg6l8X7UEj0MA2c60VSlhP0CA4x5OQ</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>Abcouwer, Steve F</creator><creator>Marjon, Philip L</creator><creator>Loper, Robyn K</creator><creator>Vander Jagt, David L</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20020801</creationdate><title>Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress</title><author>Abcouwer, Steve F ; Marjon, Philip L ; Loper, Robyn K ; Vander Jagt, David L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-d9fbc9f161a8364792625e6b35824ea37e3ec271e665c76d52e9ae23387edfae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acids - deficiency</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Hypoxia - physiology</topic><topic>Cells, Cultured</topic><topic>Endoplasmic Reticulum - physiology</topic><topic>Endothelial Growth Factors - genetics</topic><topic>Endothelial Growth Factors - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Glyceraldehyde-3-Phosphate Dehydrogenases - genetics</topic><topic>Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism</topic><topic>Heat-Shock Proteins</topic><topic>Humans</topic><topic>Lymphokines - genetics</topic><topic>Lymphokines - metabolism</topic><topic>Medical sciences</topic><topic>Molecular Chaperones - genetics</topic><topic>Molecular Chaperones - metabolism</topic><topic>Ophthalmology</topic><topic>Pigment Epithelium of Eye - metabolism</topic><topic>Retinopathies</topic><topic>RNA, Messenger - metabolism</topic><topic>Stress, Physiological - metabolism</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abcouwer, Steve F</creatorcontrib><creatorcontrib>Marjon, Philip L</creatorcontrib><creatorcontrib>Loper, Robyn K</creatorcontrib><creatorcontrib>Vander Jagt, David L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abcouwer, Steve F</au><au>Marjon, Philip L</au><au>Loper, Robyn K</au><au>Vander Jagt, David L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>43</volume><issue>8</issue><spage>2791</spage><epage>2798</epage><pages>2791-2798</pages><issn>0146-0404</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>Vascular endothelial growth factor (VEGF) plays an important role in initiation of the angiogenesis that leads to proliferative retinopathy. Several environmental conditions and chemical agents that influence the expression of VEGF can also cause endoplasmic reticulum (ER) stress. The hypothesis for the current study was that expression of VEGF is responsive to conditions that cause ER stress, including amino acid deprivation.
Confluent cultures of a human retinal pigmented epithelial cell line (ARPE-19) were deprived of amino acids or treated with chemical inducers of ER stress. Treatment with cobalt was used to mimic hypoxia-induced expression of VEGF. Northern blot analysis was used to measure intracellular VEGF mRNA, and ELISA was used to measure secreted VEGF protein. Glucose-regulated protein 78 (GRP78) mRNA levels were compared with those of VEGF. Glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA was used as a control.
Conditions and chemical agents known to activate ER stress response (ERSR) pathways also induced the expression of VEGF. Deprivation of amino acids in the culture medium increased VEGF mRNA expression by 1.3- to 6-fold. Glucose deprivation or treatment of ARPE-19 cells with tunicamycin, brefeldin A, the calcium ionophore A23187, or thapsigargin increased the expression of VEGF mRNA in these cells by 8- to 10-fold. Expression of GRP78 mRNA was well correlated with that of VEGF mRNA under all conditions. These treatments also increased the secretion of VEGF protein by up to twofold. The increase in VEGF mRNA level in response to glutamine deprivation was rapid (greater than 10-fold) and was observed in a physiologically relevant range of glutamine concentrations. The half-life of VEGF mRNA was increased 2.5-fold by glutamine starvation.
These results indicate that VEGF is an ER stress-responsive gene and suggest that cells can respond to nutrient deprivation by increasing VEGF expression through both transcriptional and posttranscriptional mechanisms.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>12147617</pmid><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0146-0404 |
| ispartof | Investigative ophthalmology & visual science, 2002-08, Vol.43 (8), p.2791-2798 |
| issn | 0146-0404 1552-5783 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71949150 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acids - deficiency Biological and medical sciences Blotting, Northern Carrier Proteins - genetics Carrier Proteins - metabolism Cell Hypoxia - physiology Cells, Cultured Endoplasmic Reticulum - physiology Endothelial Growth Factors - genetics Endothelial Growth Factors - metabolism Enzyme-Linked Immunosorbent Assay Glyceraldehyde-3-Phosphate Dehydrogenases - genetics Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism Heat-Shock Proteins Humans Lymphokines - genetics Lymphokines - metabolism Medical sciences Molecular Chaperones - genetics Molecular Chaperones - metabolism Ophthalmology Pigment Epithelium of Eye - metabolism Retinopathies RNA, Messenger - metabolism Stress, Physiological - metabolism Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| title | Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A45%3A07IST&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=Response%20of%20VEGF%20Expression%20to%20Amino%20Acid%20Deprivation%20and%20Inducers%20of%20Endoplasmic%20Reticulum%20Stress&rft.jtitle=Investigative%20ophthalmology%20&%20visual%20science&rft.au=Abcouwer,%20Steve%20F&rft.date=2002-08-01&rft.volume=43&rft.issue=8&rft.spage=2791&rft.epage=2798&rft.pages=2791-2798&rft.issn=0146-0404&rft.eissn=1552-5783&rft.coden=IOVSDA&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E71949150%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=71949150&rft_id=info:pmid/12147617&rfr_iscdi=true |