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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) 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.

Registro:

Documento: Artículo
Título:Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants
Autor:Juknat, A.A.; Kotler, M.L.; Quaglino, A.; Carrillo, N.M.; Hevor, T.
Filiación:Depto. de Quím. Biol., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Laboratoire de Physiologie Animale, Faculté des Sciences, Université d'Orléans, Orléans, France
Beruti 3244 - 4 Piso - Dto. B, C 1425 BBP, Buenos Aires, Argentina
Palabras clave:δ-aminolevulinic acid; Antioxidant enzymes; Astrocyte; Glutathione; Melatonin; Necrosis; Reactive oxygen species; aminolevulinic acid; antioxidant; caspase 3; catalase; glutathione; lipocortin 5; malonaldehyde; melatonin; porphobilinogen deaminase; porphyrin; propidium iodide; superoxide dismutase; animal cell; animal tissue; apoptosis; article; astrocyte; bioaccumulation; biosynthesis; cell damage; cell death; cell membrane; cell protection; cell structure; cell viability; controlled study; enzyme activity; incubation time; lipid peroxidation; mouse; nonhuman; Aminolevulinic Acid; Animals; Antioxidants; Astrocytes; Cell Death; Lipid Peroxidation; Melatonin; Mice; Photosensitizing Agents; Porphyrins
Año:2003
Volumen:35
Número:1
Página de inicio:1
Página de fin:11
DOI: http://dx.doi.org/10.1034/j.1600-079X.2003.00030.x
Título revista:Journal of Pineal Research
Título revista abreviado:J. Pineal Res.
ISSN:07423098
CODEN:JPRSE
CAS: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
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v35_n1_p1_Juknat

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Citas:

---------- APA ----------
Juknat, A.A., Kotler, M.L., Quaglino, A., Carrillo, N.M. & Hevor, T. (2003) . Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants. Journal of Pineal Research, 35(1), 1-11.
http://dx.doi.org/10.1034/j.1600-079X.2003.00030.x
---------- CHICAGO ----------
Juknat, A.A., Kotler, M.L., Quaglino, A., Carrillo, N.M., Hevor, T. "Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants" . Journal of Pineal Research 35, no. 1 (2003) : 1-11.
http://dx.doi.org/10.1034/j.1600-079X.2003.00030.x
---------- MLA ----------
Juknat, A.A., Kotler, M.L., Quaglino, A., Carrillo, N.M., Hevor, T. "Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants" . Journal of Pineal Research, vol. 35, no. 1, 2003, pp. 1-11.
http://dx.doi.org/10.1034/j.1600-079X.2003.00030.x
---------- VANCOUVER ----------
Juknat, A.A., Kotler, M.L., Quaglino, A., Carrillo, N.M., Hevor, T. Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants. J. Pineal Res. 2003;35(1):1-11.
http://dx.doi.org/10.1034/j.1600-079X.2003.00030.x