Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways
The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure signifi...
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| Veröffentlicht in: | Apoptosis (London) 2014-06, Vol.19 (6), p.922-932 |
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| creator | Huang, Chen Zhang, Pei Wang, Wei Xu, Yongsheng Wang, Minshu Chen, Xiaoyong Dong, Xuran |
| description | The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways. |
| doi_str_mv | 10.1007/s10495-014-0983-2 |
| format | Article |
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In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways.</description><identifier>ISSN: 1360-8185</identifier><identifier>EISSN: 1573-675X</identifier><identifier>DOI: 10.1007/s10495-014-0983-2</identifier><identifier>PMID: 24682673</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Caspase 3 - metabolism ; Cell Biology ; Cell Line ; Cell Survival - radiation effects ; Exposure ; Heme Oxygenase-1 - metabolism ; JNK Mitogen-Activated Protein Kinases - metabolism ; Light - adverse effects ; MAP Kinase Signaling System ; Mitochondria - metabolism ; Mitochondria - radiation effects ; NF-E2-Related Factor 2 - metabolism ; Oncology ; Original Paper ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells - cytology ; Retinal Ganglion Cells - metabolism ; Retinal Ganglion Cells - radiation effects ; Virology</subject><ispartof>Apoptosis (London), 2014-06, Vol.19 (6), p.922-932</ispartof><rights>Springer Science+Business Media New York 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-a68f2716a338e919b17718f25eace6e23ddeceec7f4fdcad892aaf7c036864203</citedby><cites>FETCH-LOGICAL-c438t-a68f2716a338e919b17718f25eace6e23ddeceec7f4fdcad892aaf7c036864203</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/s10495-014-0983-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10495-014-0983-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24682673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Chen</creatorcontrib><creatorcontrib>Zhang, Pei</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Xu, Yongsheng</creatorcontrib><creatorcontrib>Wang, Minshu</creatorcontrib><creatorcontrib>Chen, Xiaoyong</creatorcontrib><creatorcontrib>Dong, Xuran</creatorcontrib><title>Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways</title><title>Apoptosis (London)</title><addtitle>Apoptosis</addtitle><addtitle>Apoptosis</addtitle><description>The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Biology</subject><subject>Cell Line</subject><subject>Cell Survival - radiation effects</subject><subject>Exposure</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Light - adverse effects</subject><subject>MAP Kinase Signaling System</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - radiation effects</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Oxidative Stress</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retinal Ganglion Cells - cytology</subject><subject>Retinal Ganglion Cells - metabolism</subject><subject>Retinal Ganglion Cells - radiation effects</subject><subject>Virology</subject><issn>1360-8185</issn><issn>1573-675X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><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>eNp1kc1u1DAUhS0Eou3AA7BBltiwqMF_iR121QgKYhAIgcQu8tg3GVdJnNrO0D4Nr4qHKQghsfLVPd891_ZB6AmjLxil6mViVDYVoUwS2mhB-D10yiolSK2qb_dLLWpKNNPVCTpL6YpSKrSQD9EJl7XmtRKn6McmTD3JEEe8HRbAg-93GcPNHNISAfvJLRYS_ny5JhW2MAzYgcm7IuC9zzG8KtU-DHsYYco4dHj0OdhdmFz0hjiYYXIHxcxhziH5dI7DjXcm-z3glCOk0jGTwx8uPr3HyfeTGfzU47ks-W5u0yP0oDNDgsd35wp9ffP6y_ot2Xy8fLe-2BArhc7E1LrjitVGCA0Na7ZMKVZaFRgLNXDhHFgAqzrZOWucbrgxnbJU1LqWnIoVen70nWO4XiDldvTp8F4zQVhSyyqmueS6fPMKPfsHvQpLLPf-RalKMq1lodiRsjGkFKFr5-hHE29bRttDeu0xvbak1x7Sa3mZeXrnvGxHcH8mfsdVAH4EUpGmHuJfq__r-hNxrqfC</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Huang, Chen</creator><creator>Zhang, Pei</creator><creator>Wang, Wei</creator><creator>Xu, Yongsheng</creator><creator>Wang, Minshu</creator><creator>Chen, Xiaoyong</creator><creator>Dong, Xuran</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RQ</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways</title><author>Huang, Chen ; Zhang, Pei ; Wang, Wei ; Xu, Yongsheng ; Wang, Minshu ; Chen, Xiaoyong ; Dong, Xuran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-a68f2716a338e919b17718f25eace6e23ddeceec7f4fdcad892aaf7c036864203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Biology</topic><topic>Cell Line</topic><topic>Cell Survival - radiation effects</topic><topic>Exposure</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Light - adverse effects</topic><topic>MAP Kinase Signaling System</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - radiation effects</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Oxidative Stress</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retinal Ganglion Cells - cytology</topic><topic>Retinal Ganglion Cells - metabolism</topic><topic>Retinal Ganglion Cells - radiation effects</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Chen</creatorcontrib><creatorcontrib>Zhang, Pei</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Xu, Yongsheng</creatorcontrib><creatorcontrib>Wang, Minshu</creatorcontrib><creatorcontrib>Chen, Xiaoyong</creatorcontrib><creatorcontrib>Dong, Xuran</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Career & Technical Education Database</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Apoptosis (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Chen</au><au>Zhang, Pei</au><au>Wang, Wei</au><au>Xu, Yongsheng</au><au>Wang, Minshu</au><au>Chen, Xiaoyong</au><au>Dong, Xuran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways</atitle><jtitle>Apoptosis (London)</jtitle><stitle>Apoptosis</stitle><addtitle>Apoptosis</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>19</volume><issue>6</issue><spage>922</spage><epage>932</epage><pages>922-932</pages><issn>1360-8185</issn><eissn>1573-675X</eissn><abstract>The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly understood. In this study, we established a patented light-emitting diode-based system to study the effects of long-term blue light exposure under culture conditions on RGC-5 cells. Long-term blue light exposure significantly reduced cell viability in a time-dependent manner and induced apoptosis and necrosis in RGC-5 cells. Long-term blue light exposure marked an increase in the expression of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down-regulation, and displayed features of the mitochondria-dependent apoptosis pathway. Blue light exposure also increased the generation of reactive oxygen species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, blue light exposure constitutively activated p38 mitogen-activated protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the phosphorylation of extracellular signal-regulated kinase in the early phase, in blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was further enhanced after RGC-5 cells were exposed to blue light. Taken together, these findings indicated that blue light induced RGC-5 cell line death in dependence upon exposure duration. The potential mechanisms for this phenomenon might be via activated mitochondria-dependent apoptosis, increased ROS production and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling pathways.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>24682673</pmid><doi>10.1007/s10495-014-0983-2</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Apoptosis Biochemistry Biomedical and Life Sciences Biomedicine Cancer Research Caspase 3 - metabolism Cell Biology Cell Line Cell Survival - radiation effects Exposure Heme Oxygenase-1 - metabolism JNK Mitogen-Activated Protein Kinases - metabolism Light - adverse effects MAP Kinase Signaling System Mitochondria - metabolism Mitochondria - radiation effects NF-E2-Related Factor 2 - metabolism Oncology Original Paper Oxidative Stress Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Rats, Sprague-Dawley Retinal Ganglion Cells - cytology Retinal Ganglion Cells - metabolism Retinal Ganglion Cells - radiation effects Virology |
| title | Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways |
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