UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium
To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts. The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were har...
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| creator | Yang, Jing Zhou, Sheng Gu, Jianjun Guo, Minfei Xia, Honghui Liu, Yizhi |
| description | To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts.
The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6.
In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control.
These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract. |
| doi_str_mv | 10.1371/journal.pone.0137582 |
| format | Article |
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The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6.
In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control.
These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0137582</identifier><identifier>PMID: 26351848</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Adult ; Age ; alpha-Crystallin A Chain - biosynthesis ; alpha-Crystallin A Chain - genetics ; alpha-Crystallin B Chain - biosynthesis ; alpha-Crystallin B Chain - genetics ; Cataract - complications ; Cataract - genetics ; Cataract - pathology ; Cataracts ; Cell cycle ; Crystal structure ; Crystallin ; Crystallinity ; Endoplasmic reticulum ; Endoplasmic Reticulum - metabolism ; Epithelial cells ; Epithelium ; Epithelium - metabolism ; Epithelium - pathology ; Eye (anatomy) ; Eye lens ; Female ; Gene expression ; Gene Expression Regulation ; Genes ; Humans ; Kinases ; Laboratories ; Lenses ; Localization ; Male ; Middle Aged ; Myopia ; Myopia - complications ; Myopia - genetics ; Myopia - pathology ; Patients ; Protein folding ; Protein synthesis ; Proteomics ; Signal transduction ; Surgery ; Transcription factors ; Trauma ; Unfolded Protein Response - genetics</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0137582-e0137582</ispartof><rights>2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Yang et al 2015 Yang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-9722e318964398ccbbea09cae5be95e51c05b1cbc3842f9c6573240f69898e113</citedby><cites>FETCH-LOGICAL-c526t-9722e318964398ccbbea09cae5be95e51c05b1cbc3842f9c6573240f69898e113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564188/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564188/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26351848$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Jing</creatorcontrib><creatorcontrib>Zhou, Sheng</creatorcontrib><creatorcontrib>Gu, Jianjun</creatorcontrib><creatorcontrib>Guo, Minfei</creatorcontrib><creatorcontrib>Xia, Honghui</creatorcontrib><creatorcontrib>Liu, Yizhi</creatorcontrib><title>UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts.
The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6.
In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control.
These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.</description><subject>Activation</subject><subject>Adult</subject><subject>Age</subject><subject>alpha-Crystallin A Chain - biosynthesis</subject><subject>alpha-Crystallin A Chain - genetics</subject><subject>alpha-Crystallin B Chain - biosynthesis</subject><subject>alpha-Crystallin B Chain - genetics</subject><subject>Cataract - complications</subject><subject>Cataract - genetics</subject><subject>Cataract - pathology</subject><subject>Cataracts</subject><subject>Cell cycle</subject><subject>Crystal structure</subject><subject>Crystallin</subject><subject>Crystallinity</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Epithelium - metabolism</subject><subject>Epithelium - pathology</subject><subject>Eye (anatomy)</subject><subject>Eye lens</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Humans</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lenses</subject><subject>Localization</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myopia</subject><subject>Myopia - complications</subject><subject>Myopia - genetics</subject><subject>Myopia - pathology</subject><subject>Patients</subject><subject>Protein folding</subject><subject>Protein synthesis</subject><subject>Proteomics</subject><subject>Signal transduction</subject><subject>Surgery</subject><subject>Transcription factors</subject><subject>Trauma</subject><subject>Unfolded Protein Response - genetics</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUt1qFDEYHUSxtfoGogFvvJk1_5vcCGWttrCiFHsdMpnMbpbMZEwylX0sX8RnMu1OSytCSD5Ozjn5vnCq6jWCC0SW6MMuTHHQfjGGwS5ggZjAT6pjJAmuOYbk6YP6qHqR0g5CRgTnz6sjzAlDgorjqr_6fglOTXbXOrswAD20IG8t-BR-DfWl3Uz-gIcO_Pldr-I-Ze29G0BZ51Ovy-42W_B1H0ani6DQbQtWOuuoTQZrOyRwNrpi6d3Uv6yeddon-2o-T6qrz2c_Vuf1-tuXi9XpujYM81zLJcaWICE5JVIY0zRWQ2m0ZY2VzDJkIGuQaQwRFHfScLYkmMKOSyGFRYicVG8PvqMPSc0_lRRaIigFppQWxsWB0Qa9U2N0vY57FbRTt0CIG6VjdsZbhRGymJlWcoOoIFq2zHSGa4mQaRvJi9fH-bWp6W1r7JCj9o9MH98Mbqs24VpRxikSohi8nw1i-DnZlFXvkrHe68GG6bZvxChhBBfqu3-o_5-OHlgmhpSi7e6bQVDdpOdOpW7So-b0FNmbh4Pci-7iQv4C7aDDiw</recordid><startdate>20150909</startdate><enddate>20150909</enddate><creator>Yang, Jing</creator><creator>Zhou, Sheng</creator><creator>Gu, Jianjun</creator><creator>Guo, Minfei</creator><creator>Xia, Honghui</creator><creator>Liu, Yizhi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150909</creationdate><title>UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium</title><author>Yang, Jing ; Zhou, Sheng ; Gu, Jianjun ; Guo, Minfei ; Xia, Honghui ; Liu, Yizhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-9722e318964398ccbbea09cae5be95e51c05b1cbc3842f9c6573240f69898e113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Activation</topic><topic>Adult</topic><topic>Age</topic><topic>alpha-Crystallin A Chain - biosynthesis</topic><topic>alpha-Crystallin A Chain - genetics</topic><topic>alpha-Crystallin B Chain - biosynthesis</topic><topic>alpha-Crystallin B Chain - genetics</topic><topic>Cataract - complications</topic><topic>Cataract - genetics</topic><topic>Cataract - pathology</topic><topic>Cataracts</topic><topic>Cell cycle</topic><topic>Crystal structure</topic><topic>Crystallin</topic><topic>Crystallinity</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Epithelium - metabolism</topic><topic>Epithelium - pathology</topic><topic>Eye (anatomy)</topic><topic>Eye lens</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Humans</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Lenses</topic><topic>Localization</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myopia</topic><topic>Myopia - complications</topic><topic>Myopia - genetics</topic><topic>Myopia - pathology</topic><topic>Patients</topic><topic>Protein folding</topic><topic>Protein synthesis</topic><topic>Proteomics</topic><topic>Signal transduction</topic><topic>Surgery</topic><topic>Transcription factors</topic><topic>Trauma</topic><topic>Unfolded Protein Response - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Jing</creatorcontrib><creatorcontrib>Zhou, Sheng</creatorcontrib><creatorcontrib>Gu, Jianjun</creatorcontrib><creatorcontrib>Guo, Minfei</creatorcontrib><creatorcontrib>Xia, Honghui</creatorcontrib><creatorcontrib>Liu, Yizhi</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Jing</au><au>Zhou, Sheng</au><au>Gu, Jianjun</au><au>Guo, Minfei</au><au>Xia, Honghui</au><au>Liu, Yizhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-09</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0137582</spage><epage>e0137582</epage><pages>e0137582-e0137582</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts.
The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6.
In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control.
These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26351848</pmid><doi>10.1371/journal.pone.0137582</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Adult Age alpha-Crystallin A Chain - biosynthesis alpha-Crystallin A Chain - genetics alpha-Crystallin B Chain - biosynthesis alpha-Crystallin B Chain - genetics Cataract - complications Cataract - genetics Cataract - pathology Cataracts Cell cycle Crystal structure Crystallin Crystallinity Endoplasmic reticulum Endoplasmic Reticulum - metabolism Epithelial cells Epithelium Epithelium - metabolism Epithelium - pathology Eye (anatomy) Eye lens Female Gene expression Gene Expression Regulation Genes Humans Kinases Laboratories Lenses Localization Male Middle Aged Myopia Myopia - complications Myopia - genetics Myopia - pathology Patients Protein folding Protein synthesis Proteomics Signal transduction Surgery Transcription factors Trauma Unfolded Protein Response - genetics |
| title | UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium |
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