A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration
Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening dis...
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| description | Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye. |
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These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0041309</identifier><identifier>PMID: 22829938</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Age related diseases ; Aging ; Aldehydes ; Arteriosclerosis ; Atherosclerosis ; Biology ; Cells, Cultured ; Chemical compounds ; Chemistry ; Chromatography ; Chromatography, Liquid ; Chronic illnesses ; Diabetes ; Diabetes mellitus ; Enzyme-Linked Immunosorbent Assay ; Eye ; Fluorescence ; Fluorophores ; Glycation End Products, Advanced - metabolism ; Glycoproteins ; Glycosylation ; Glyoxal ; Glyoxal - metabolism ; Guanidines - metabolism ; Humans ; Ionization ; Irradiation ; Lipofuscin - metabolism ; Liquid chromatography ; Macular degeneration ; Macular Degeneration - metabolism ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Oxidation ; Oxidative stress ; Phenylhydrazines - metabolism ; Photodegradation ; Photooxidation ; Photosensitivity ; Physiological aspects ; Pigments ; Proteins ; Pyridinium Compounds - metabolism ; Pyruvaldehyde ; Pyruvaldehyde - metabolism ; Radiation ; Retina ; Retina - metabolism ; Retina - pathology ; Retinal Drusen - metabolism ; Retinaldehyde - analogs & derivatives ; Retinaldehyde - metabolism ; Retinoids - metabolism ; Rodents ; Spectrometry, Mass, Electrospray Ionization ; Structure-function relationships</subject><ispartof>PloS one, 2012-07, Vol.7 (7), p.e41309-e41309</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Yoon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Yoon et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-dfcaf235e6e2817d435e41f6cf6174532027f4e23d42088281fb5361dc09237b3</citedby><cites>FETCH-LOGICAL-c692t-dfcaf235e6e2817d435e41f6cf6174532027f4e23d42088281fb5361dc09237b3</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/PMC3400616/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400616/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22829938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lewin, Alfred</contributor><creatorcontrib>Yoon, Kee Dong</creatorcontrib><creatorcontrib>Yamamoto, Kazunori</creatorcontrib><creatorcontrib>Ueda, Keiko</creatorcontrib><creatorcontrib>Zhou, Jilin</creatorcontrib><creatorcontrib>Sparrow, Janet R</creatorcontrib><title>A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.</description><subject>Age</subject><subject>Age related diseases</subject><subject>Aging</subject><subject>Aldehydes</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biology</subject><subject>Cells, Cultured</subject><subject>Chemical compounds</subject><subject>Chemistry</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Chronic illnesses</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Eye</subject><subject>Fluorescence</subject><subject>Fluorophores</subject><subject>Glycation End Products, Advanced - metabolism</subject><subject>Glycoproteins</subject><subject>Glycosylation</subject><subject>Glyoxal</subject><subject>Glyoxal - metabolism</subject><subject>Guanidines - metabolism</subject><subject>Humans</subject><subject>Ionization</subject><subject>Irradiation</subject><subject>Lipofuscin - metabolism</subject><subject>Liquid chromatography</subject><subject>Macular degeneration</subject><subject>Macular Degeneration - metabolism</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Phenylhydrazines - metabolism</subject><subject>Photodegradation</subject><subject>Photooxidation</subject><subject>Photosensitivity</subject><subject>Physiological aspects</subject><subject>Pigments</subject><subject>Proteins</subject><subject>Pyridinium Compounds - metabolism</subject><subject>Pyruvaldehyde</subject><subject>Pyruvaldehyde - metabolism</subject><subject>Radiation</subject><subject>Retina</subject><subject>Retina - metabolism</subject><subject>Retina - pathology</subject><subject>Retinal Drusen - 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novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration</title><author>Yoon, Kee Dong ; Yamamoto, Kazunori ; Ueda, Keiko ; Zhou, Jilin ; Sparrow, Janet R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-dfcaf235e6e2817d435e41f6cf6174532027f4e23d42088281fb5361dc09237b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Age</topic><topic>Age related diseases</topic><topic>Aging</topic><topic>Aldehydes</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Biology</topic><topic>Cells, Cultured</topic><topic>Chemical compounds</topic><topic>Chemistry</topic><topic>Chromatography</topic><topic>Chromatography, Liquid</topic><topic>Chronic illnesses</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Enzyme-Linked Immunosorbent 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One</addtitle><date>2012-07-19</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e41309</spage><epage>e41309</epage><pages>e41309-e41309</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22829938</pmid><doi>10.1371/journal.pone.0041309</doi><tpages>e41309</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-07, Vol.7 (7), p.e41309-e41309 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | PLoS (Open access); MEDLINE; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library |
| subjects | Age Age related diseases Aging Aldehydes Arteriosclerosis Atherosclerosis Biology Cells, Cultured Chemical compounds Chemistry Chromatography Chromatography, Liquid Chronic illnesses Diabetes Diabetes mellitus Enzyme-Linked Immunosorbent Assay Eye Fluorescence Fluorophores Glycation End Products, Advanced - metabolism Glycoproteins Glycosylation Glyoxal Glyoxal - metabolism Guanidines - metabolism Humans Ionization Irradiation Lipofuscin - metabolism Liquid chromatography Macular degeneration Macular Degeneration - metabolism Mass spectrometry Mass spectroscopy Medicine Oxidation Oxidative stress Phenylhydrazines - metabolism Photodegradation Photooxidation Photosensitivity Physiological aspects Pigments Proteins Pyridinium Compounds - metabolism Pyruvaldehyde Pyruvaldehyde - metabolism Radiation Retina Retina - metabolism Retina - pathology Retinal Drusen - metabolism Retinaldehyde - analogs & derivatives Retinaldehyde - metabolism Retinoids - metabolism Rodents Spectrometry, Mass, Electrospray Ionization Structure-function relationships |
| title | A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T18%3A31%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20source%20of%20methylglyoxal%20and%20glyoxal%20in%20retina:%20implications%20for%20age-related%20macular%20degeneration&rft.jtitle=PloS%20one&rft.au=Yoon,%20Kee%20Dong&rft.date=2012-07-19&rft.volume=7&rft.issue=7&rft.spage=e41309&rft.epage=e41309&rft.pages=e41309-e41309&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0041309&rft_dat=%3Cgale_plos_%3EA477065175%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326219930&rft_id=info:pmid/22829938&rft_galeid=A477065175&rft_doaj_id=oai_doaj_org_article_a3ce3385d1f64dee85a971713d0e1f76&rfr_iscdi=true |