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 rever...

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Autor principal: Juknat, A.A
Otros Autores: Kotler, M.L, Quaglino, A., Carrillo, N.M, Hevor, T.
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Lenguaje:Inglés
Publicado: 2003
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024 7 |2 scopus  |a 2-s2.0-0037670869 
024 7 |2 cas  |a aminolevulinic acid, 106-60-5; caspase 3, 169592-56-7; catalase, 9001-05-2; glutathione, 70-18-8; lipocortin 5, 111237-10-6; malonaldehyde, 542-78-9; melatonin, 73-31-4; porphobilinogen deaminase, 9036-47-9, 9074-91-3; porphyrin, 24869-67-8; propidium iodide, 25535-16-4; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; Aminolevulinic Acid, 106-60-5; Antioxidants; Melatonin, 73-31-4; Photosensitizing Agents; Porphyrins 
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100 1 |a Juknat, A.A. 
245 1 0 |a Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants 
260 |c 2003 
270 1 0 |m Juknat, A.A.Beruti 3244 - 4 Piso - Dto. B, C 1425 BBP, Buenos Aires, Argentina; email: aajuknat@mail.retina.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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) x 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.  |l eng 
593 |a Depto. de Quím. Biol., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Laboratoire de Physiologie Animale, Faculté des Sciences, Université d'Orléans, Orléans, France 
593 |a Beruti 3244 - 4 Piso - Dto. B, C 1425 BBP, Buenos Aires, Argentina 
690 1 0 |a Δ-AMINOLEVULINIC ACID 
690 1 0 |a ANTIOXIDANT ENZYMES 
690 1 0 |a ASTROCYTE 
690 1 0 |a GLUTATHIONE 
690 1 0 |a MELATONIN 
690 1 0 |a REACTIVE OXYGEN SPECIES 
690 1 0 |a AMINOLEVULINIC ACID 
690 1 0 |a ANTIOXIDANT 
690 1 0 |a CASPASE 3 
690 1 0 |a CATALASE 
690 1 0 |a GLUTATHIONE 
690 1 0 |a LIPOCORTIN 5 
690 1 0 |a MALONALDEHYDE 
690 1 0 |a MELATONIN 
690 1 0 |a PORPHOBILINOGEN DEAMINASE 
690 1 0 |a PORPHYRIN 
690 1 0 |a PROPIDIUM IODIDE 
690 1 0 |a SUPEROXIDE DISMUTASE 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a ASTROCYTE 
690 1 0 |a BIOACCUMULATION 
690 1 0 |a BIOSYNTHESIS 
690 1 0 |a CELL DAMAGE 
690 1 0 |a CELL DEATH 
690 1 0 |a CELL MEMBRANE 
690 1 0 |a CELL PROTECTION 
690 1 0 |a CELL STRUCTURE 
690 1 0 |a CELL VIABILITY 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a ENZYME ACTIVITY 
690 1 0 |a INCUBATION TIME 
690 1 0 |a LIPID PEROXIDATION 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a AMINOLEVULINIC ACID 
690 1 0 |a ANIMALS 
690 1 0 |a ANTIOXIDANTS 
690 1 0 |a ASTROCYTES 
690 1 0 |a CELL DEATH 
690 1 0 |a LIPID PEROXIDATION 
690 1 0 |a MELATONIN 
690 1 0 |a MICE 
690 1 0 |a PHOTOSENSITIZING AGENTS 
690 1 0 |a PORPHYRINS 
650 1 7 |2 spines  |a NECROSIS 
700 1 |a Kotler, M.L. 
700 1 |a Quaglino, A. 
700 1 |a Carrillo, N.M. 
700 1 |a Hevor, T. 
773 0 |d 2003  |g v. 35  |h pp. 1-11  |k n. 1  |p J. Pineal Res.  |x 07423098  |t Journal of Pineal Research 
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856 4 0 |u https://hdl.handle.net/20.500.12110/paper_07423098_v35_n1_p1_Juknat  |y Handle 
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