Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐trans‐retinal
All‐trans‐retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11‐cis‐retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4‐associated autosomal recess...
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| creator | Cubizolle, Aurélie Cia, David Moine, Espérance Jacquemot, Nathalie Guillou, Laurent Rosell, Mélissa Angebault‐Prouteau, Claire Lenaers, Guy Meunier, Isabelle Vercauteren, Joseph Durand, Thierry Crauste, Céline Brabet, Philippe |
| description | All‐trans‐retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11‐cis‐retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4‐associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E‐accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl‐phloroglucinol linked to DHA, referred to as IP‐DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE‐19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP‐DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP‐DHA applies to the mitochondrial respiration. IP‐DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP‐DHA in retinal cells involves both anti‐carbonyl and anti‐oxidative capacities. |
| doi_str_mv | 10.1111/jcmm.15135 |
| format | Article |
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It is generated by photoisomerization of 11‐cis‐retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4‐associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E‐accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl‐phloroglucinol linked to DHA, referred to as IP‐DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE‐19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP‐DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP‐DHA applies to the mitochondrial respiration. IP‐DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP‐DHA in retinal cells involves both anti‐carbonyl and anti‐oxidative capacities.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.15135</identifier><identifier>PMID: 32212312</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>all‐trans‐retinal ; Animals ; Antioxidants ; Apoptosis ; bisretinoid A2E ; Carbonyl compounds ; carbonyl stress ; Catalase ; Cell culture ; Cell Line ; Cell Survival ; Chemical Sciences ; Chromophores ; Dehydroepiandrosterone ; Dystrophy ; Epithelium ; Fatty acids ; Humans ; isopropyl‐phloroglucinol‐DHA conjugate ; Lethal dose ; Light ; Lipofuscin ; Membranes ; Mice ; Mitochondria ; Neurons ; Organic chemistry ; Original ; outer retina cells ; Oxidative Stress ; Oxygen ; Phenol ; Phloroglucinol ; Phosphatidylethanolamine ; Photooxidation ; Photoreceptors ; Pigmentation ; Pigments ; Polyphenols ; Polyunsaturated fatty acids ; Protective Agents ; Rats ; Reactive Oxygen Species ; Respiration ; Retina ; Retinal Pigment Epithelium ; Retinaldehyde ; Retinoids ; Structure-Activity Relationship ; Toxicity</subject><ispartof>Journal of cellular and molecular medicine, 2020-05, Vol.24 (9), p.5057-5069</ispartof><rights>2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4825-90e11c8d2bcdf8684dc10a54218f01b124faae5119b09356e1c01cca909ed5133</citedby><cites>FETCH-LOGICAL-c4825-90e11c8d2bcdf8684dc10a54218f01b124faae5119b09356e1c01cca909ed5133</cites><orcidid>0000-0003-2739-1622 ; 0000-0003-2736-3349 ; 0000-0001-6086-7296 ; 0000-0002-5714-8749 ; 0000-0002-1146-7904</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205824/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205824/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1416,11561,27923,27924,45573,45574,46051,46475,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32212312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02593070$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Cubizolle, Aurélie</creatorcontrib><creatorcontrib>Cia, David</creatorcontrib><creatorcontrib>Moine, Espérance</creatorcontrib><creatorcontrib>Jacquemot, Nathalie</creatorcontrib><creatorcontrib>Guillou, Laurent</creatorcontrib><creatorcontrib>Rosell, Mélissa</creatorcontrib><creatorcontrib>Angebault‐Prouteau, Claire</creatorcontrib><creatorcontrib>Lenaers, Guy</creatorcontrib><creatorcontrib>Meunier, Isabelle</creatorcontrib><creatorcontrib>Vercauteren, Joseph</creatorcontrib><creatorcontrib>Durand, Thierry</creatorcontrib><creatorcontrib>Crauste, Céline</creatorcontrib><creatorcontrib>Brabet, Philippe</creatorcontrib><title>Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐trans‐retinal</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>All‐trans‐retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11‐cis‐retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4‐associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E‐accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl‐phloroglucinol linked to DHA, referred to as IP‐DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE‐19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP‐DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP‐DHA applies to the mitochondrial respiration. IP‐DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP‐DHA in retinal cells involves both anti‐carbonyl and anti‐oxidative capacities.</description><subject>all‐trans‐retinal</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>bisretinoid A2E</subject><subject>Carbonyl compounds</subject><subject>carbonyl stress</subject><subject>Catalase</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell Survival</subject><subject>Chemical Sciences</subject><subject>Chromophores</subject><subject>Dehydroepiandrosterone</subject><subject>Dystrophy</subject><subject>Epithelium</subject><subject>Fatty acids</subject><subject>Humans</subject><subject>isopropyl‐phloroglucinol‐DHA conjugate</subject><subject>Lethal dose</subject><subject>Light</subject><subject>Lipofuscin</subject><subject>Membranes</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Neurons</subject><subject>Organic chemistry</subject><subject>Original</subject><subject>outer retina cells</subject><subject>Oxidative Stress</subject><subject>Oxygen</subject><subject>Phenol</subject><subject>Phloroglucinol</subject><subject>Phosphatidylethanolamine</subject><subject>Photooxidation</subject><subject>Photoreceptors</subject><subject>Pigmentation</subject><subject>Pigments</subject><subject>Polyphenols</subject><subject>Polyunsaturated fatty acids</subject><subject>Protective Agents</subject><subject>Rats</subject><subject>Reactive Oxygen Species</subject><subject>Respiration</subject><subject>Retina</subject><subject>Retinal Pigment Epithelium</subject><subject>Retinaldehyde</subject><subject>Retinoids</subject><subject>Structure-Activity 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protects outer retinal cells against lethal dose of all‐trans‐retinal</title><author>Cubizolle, Aurélie ; Cia, David ; Moine, Espérance ; Jacquemot, Nathalie ; Guillou, Laurent ; Rosell, Mélissa ; Angebault‐Prouteau, Claire ; Lenaers, Guy ; Meunier, Isabelle ; Vercauteren, Joseph ; Durand, Thierry ; Crauste, Céline ; Brabet, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4825-90e11c8d2bcdf8684dc10a54218f01b124faae5119b09356e1c01cca909ed5133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>all‐trans‐retinal</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>bisretinoid A2E</topic><topic>Carbonyl compounds</topic><topic>carbonyl stress</topic><topic>Catalase</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell Survival</topic><topic>Chemical Sciences</topic><topic>Chromophores</topic><topic>Dehydroepiandrosterone</topic><topic>Dystrophy</topic><topic>Epithelium</topic><topic>Fatty acids</topic><topic>Humans</topic><topic>isopropyl‐phloroglucinol‐DHA conjugate</topic><topic>Lethal dose</topic><topic>Light</topic><topic>Lipofuscin</topic><topic>Membranes</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Neurons</topic><topic>Organic chemistry</topic><topic>Original</topic><topic>outer retina cells</topic><topic>Oxidative Stress</topic><topic>Oxygen</topic><topic>Phenol</topic><topic>Phloroglucinol</topic><topic>Phosphatidylethanolamine</topic><topic>Photooxidation</topic><topic>Photoreceptors</topic><topic>Pigmentation</topic><topic>Pigments</topic><topic>Polyphenols</topic><topic>Polyunsaturated fatty acids</topic><topic>Protective Agents</topic><topic>Rats</topic><topic>Reactive Oxygen Species</topic><topic>Respiration</topic><topic>Retina</topic><topic>Retinal Pigment 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Isabelle</au><au>Vercauteren, Joseph</au><au>Durand, Thierry</au><au>Crauste, Céline</au><au>Brabet, Philippe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐trans‐retinal</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2020-05</date><risdate>2020</risdate><volume>24</volume><issue>9</issue><spage>5057</spage><epage>5069</epage><pages>5057-5069</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>All‐trans‐retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11‐cis‐retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4‐associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE). This A2E‐accumulation presents as lipofuscin fluorescent pigment, and its photooxidation causes subsequent damage. Here we describe protection against a lethal dose of atRAL in both photoreceptors and RPE in primary cultures by a lipidic polyphenol derivative, an isopropyl‐phloroglucinol linked to DHA, referred to as IP‐DHA. Next, we addressed the cellular and molecular defence mechanisms in commonly used human ARPE‐19 cells. We determined that both polyunsaturated fatty acid and isopropyl substituents bond to phloroglucinol are essential to confer the highest protection. IP‐DHA responds rapidly against the toxicity of atRAL and its protective effect persists. This healthy effect of IP‐DHA applies to the mitochondrial respiration. IP‐DHA also rescues RPE cells subjected to the toxic effects of A2E after blue light exposure. Together, our findings suggest that the beneficial role of IP‐DHA in retinal cells involves both anti‐carbonyl and anti‐oxidative capacities.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32212312</pmid><doi>10.1111/jcmm.15135</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2739-1622</orcidid><orcidid>https://orcid.org/0000-0003-2736-3349</orcidid><orcidid>https://orcid.org/0000-0001-6086-7296</orcidid><orcidid>https://orcid.org/0000-0002-5714-8749</orcidid><orcidid>https://orcid.org/0000-0002-1146-7904</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1582-1838 |
| ispartof | Journal of cellular and molecular medicine, 2020-05, Vol.24 (9), p.5057-5069 |
| issn | 1582-1838 1582-4934 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; Wiley-Blackwell Open Access Titles; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; PubMed Central |
| subjects | all‐trans‐retinal Animals Antioxidants Apoptosis bisretinoid A2E Carbonyl compounds carbonyl stress Catalase Cell culture Cell Line Cell Survival Chemical Sciences Chromophores Dehydroepiandrosterone Dystrophy Epithelium Fatty acids Humans isopropyl‐phloroglucinol‐DHA conjugate Lethal dose Light Lipofuscin Membranes Mice Mitochondria Neurons Organic chemistry Original outer retina cells Oxidative Stress Oxygen Phenol Phloroglucinol Phosphatidylethanolamine Photooxidation Photoreceptors Pigmentation Pigments Polyphenols Polyunsaturated fatty acids Protective Agents Rats Reactive Oxygen Species Respiration Retina Retinal Pigment Epithelium Retinaldehyde Retinoids Structure-Activity Relationship Toxicity |
| title | Isopropyl‐phloroglucinol‐DHA protects outer retinal cells against lethal dose of all‐trans‐retinal |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T22%3A34%3A53IST&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=Isopropyl%E2%80%90phloroglucinol%E2%80%90DHA%20protects%20outer%20retinal%20cells%20against%20lethal%20dose%20of%20all%E2%80%90trans%E2%80%90retinal&rft.jtitle=Journal%20of%20cellular%20and%20molecular%20medicine&rft.au=Cubizolle,%20Aur%C3%A9lie&rft.date=2020-05&rft.volume=24&rft.issue=9&rft.spage=5057&rft.epage=5069&rft.pages=5057-5069&rft.issn=1582-1838&rft.eissn=1582-4934&rft_id=info:doi/10.1111/jcmm.15135&rft_dat=%3Cproquest_pubme%3E2618131523%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=2618131523&rft_id=info:pmid/32212312&rfr_iscdi=true |