Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants
: Accumulation of δ‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to rev...
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description | : Accumulation of δ‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA‐promoted damage, by incubating mouse astrocytes with 1.0 mm ALA for different times (1–4 hr) in the presence of melatonin (2.5 mm), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mm). The defined relative index [(malondialdehyde levels/accumulated ALA) × 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA‐promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3‐like activity was detected. These findings provide the first experimental evidence of the involvement of ALA‐promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology. |
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Protective role of melatonin and other antioxidants</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Juknat, Adela Ana ; Kotler, Mónica Lidia ; Quaglino, Ana ; Carrillo, Natalia Marco ; Hevor, Tobias</creator><creatorcontrib>Juknat, Adela Ana ; Kotler, Mónica Lidia ; Quaglino, Ana ; Carrillo, Natalia Marco ; Hevor, Tobias</creatorcontrib><description>: Accumulation of δ‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA‐promoted damage, by incubating mouse astrocytes with 1.0 mm ALA for different times (1–4 hr) in the presence of melatonin (2.5 mm), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mm). The defined relative index [(malondialdehyde levels/accumulated ALA) × 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA‐promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3‐like activity was detected. These findings provide the first experimental evidence of the involvement of ALA‐promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology.</description><identifier>ISSN: 0742-3098</identifier><identifier>EISSN: 1600-079X</identifier><identifier>DOI: 10.1034/j.1600-079X.2003.00030.x</identifier><identifier>PMID: 12823607</identifier><identifier>CODEN: JPRSE9</identifier><language>eng</language><publisher>Oxford, UK: Munksgaard International Publishers</publisher><subject>Ageing, cell death ; Aminolevulinic Acid - pharmacology ; Animals ; antioxidant enzymes ; Antioxidants - pharmacology ; astrocyte ; Astrocytes - drug effects ; Biological and medical sciences ; Cell Death - drug effects ; Cell physiology ; Fundamental and applied biological sciences. Psychology ; glutathione ; Lipid Peroxidation - physiology ; melatonin ; Melatonin - pharmacology ; Mice ; Molecular and cellular biology ; necrosis ; Photosensitizing Agents - pharmacology ; Porphyrins - biosynthesis ; reactive oxygen species ; δ-aminolevulinic acid</subject><ispartof>Journal of pineal research, 2003-08, Vol.35 (1), p.1-11</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4630-47902ac09c464e675abb72d50504217d7532252391dd251c3ba4c7d67658a4c3</citedby><cites>FETCH-LOGICAL-c4630-47902ac09c464e675abb72d50504217d7532252391dd251c3ba4c7d67658a4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1034%2Fj.1600-079X.2003.00030.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1034%2Fj.1600-079X.2003.00030.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14940935$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12823607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Juknat, Adela Ana</creatorcontrib><creatorcontrib>Kotler, Mónica Lidia</creatorcontrib><creatorcontrib>Quaglino, Ana</creatorcontrib><creatorcontrib>Carrillo, Natalia Marco</creatorcontrib><creatorcontrib>Hevor, Tobias</creatorcontrib><title>Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants</title><title>Journal of pineal research</title><addtitle>J Pineal Res</addtitle><description>: Accumulation of δ‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA‐promoted damage, by incubating mouse astrocytes with 1.0 mm ALA for different times (1–4 hr) in the presence of melatonin (2.5 mm), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mm). The defined relative index [(malondialdehyde levels/accumulated ALA) × 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA‐promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3‐like activity was detected. These findings provide the first experimental evidence of the involvement of ALA‐promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology.</description><subject>Ageing, cell death</subject><subject>Aminolevulinic Acid - pharmacology</subject><subject>Animals</subject><subject>antioxidant enzymes</subject><subject>Antioxidants - pharmacology</subject><subject>astrocyte</subject><subject>Astrocytes - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell Death - drug effects</subject><subject>Cell physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>glutathione</subject><subject>Lipid Peroxidation - physiology</subject><subject>melatonin</subject><subject>Melatonin - pharmacology</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>necrosis</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Porphyrins - biosynthesis</subject><subject>reactive oxygen species</subject><subject>δ-aminolevulinic acid</subject><issn>0742-3098</issn><issn>1600-079X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhS0EoqHwCsgb2M1wxz9jj8QGVaUtqkKQItqd5diO6jA_xfaUZMNT9Tn6THhI1C5h43ssf-fa1wchXEFZAWUfNmVVAxQgmuuSANAS8gLl9hmaPR48RzMQjBQUGnmEXsW4yZCUsn6JjioiCa1BzNDvuTNhSN5g49oWW6fTDfa9HY2zeLXDD_eF7nw_tO5ubH2fOW28zQTuhjE6rGMKg9klF0u8yI2cSf7O4ZANeFjjzrU6DX3GdW_xkG5cyCr5YettrvE1erHWbXRvDvUYLT-fLk_Oi8uvZxcnny4Lw2oKBRMNEG2gyVvmasH1aiWI5cCBkUpYwSkhnNCmspbwytCVZkbYWtRcZkWP0ft929sw_BxdTKrzcRpY9y6PoQRlFYda_hOsZEMJcJpBuQfz78UY3FrdBt_psFMVqCkjtVFTFGqKQk0Zqb8ZqW22vj3cMa46Z5-Mh1Ay8O4A6Gh0uw66Nz4-caxh0FCeuY977pdv3e6_H6C-LC6yyPZib_cxue2jXYcfqhZUcHU1P1PfFufX3-fySi3pH4FsvaY</recordid><startdate>200308</startdate><enddate>200308</enddate><creator>Juknat, Adela Ana</creator><creator>Kotler, Mónica Lidia</creator><creator>Quaglino, Ana</creator><creator>Carrillo, Natalia Marco</creator><creator>Hevor, Tobias</creator><general>Munksgaard International Publishers</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>200308</creationdate><title>Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants</title><author>Juknat, Adela Ana ; Kotler, Mónica Lidia ; Quaglino, Ana ; Carrillo, Natalia Marco ; Hevor, Tobias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4630-47902ac09c464e675abb72d50504217d7532252391dd251c3ba4c7d67658a4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Ageing, cell death</topic><topic>Aminolevulinic Acid - pharmacology</topic><topic>Animals</topic><topic>antioxidant enzymes</topic><topic>Antioxidants - pharmacology</topic><topic>astrocyte</topic><topic>Astrocytes - drug effects</topic><topic>Biological and medical sciences</topic><topic>Cell Death - drug effects</topic><topic>Cell physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>glutathione</topic><topic>Lipid Peroxidation - physiology</topic><topic>melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>necrosis</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Porphyrins - biosynthesis</topic><topic>reactive oxygen species</topic><topic>δ-aminolevulinic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Juknat, Adela Ana</creatorcontrib><creatorcontrib>Kotler, Mónica Lidia</creatorcontrib><creatorcontrib>Quaglino, Ana</creatorcontrib><creatorcontrib>Carrillo, Natalia Marco</creatorcontrib><creatorcontrib>Hevor, Tobias</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pineal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Juknat, Adela Ana</au><au>Kotler, Mónica Lidia</au><au>Quaglino, Ana</au><au>Carrillo, Natalia Marco</au><au>Hevor, Tobias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants</atitle><jtitle>Journal of pineal research</jtitle><addtitle>J Pineal Res</addtitle><date>2003-08</date><risdate>2003</risdate><volume>35</volume><issue>1</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0742-3098</issn><eissn>1600-079X</eissn><coden>JPRSE9</coden><abstract>: Accumulation of δ‐aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA‐promoted damage, by incubating mouse astrocytes with 1.0 mm ALA for different times (1–4 hr) in the presence of melatonin (2.5 mm), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mm). The defined relative index [(malondialdehyde levels/accumulated ALA) × 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA‐promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3‐like activity was detected. 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subjects | Ageing, cell death Aminolevulinic Acid - pharmacology Animals antioxidant enzymes Antioxidants - pharmacology astrocyte Astrocytes - drug effects Biological and medical sciences Cell Death - drug effects Cell physiology Fundamental and applied biological sciences. Psychology glutathione Lipid Peroxidation - physiology melatonin Melatonin - pharmacology Mice Molecular and cellular biology necrosis Photosensitizing Agents - pharmacology Porphyrins - biosynthesis reactive oxygen species δ-aminolevulinic acid |
title | Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
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