Abstract:
Rodents treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) are a model of two hepatic toxic manifestations: porphyria and the appearance of hepatic cytoplasmic protein aggregates (Mallory-Denk Bodies, MDBs). MDBs are induced after long-term DDC feeding, consist primarily of keratins 8 and 18, and contain glutamine-lysine cross-links generated by transglutaminases (TGs). TGs are Ca2+-dependent enzymes which catalyze the formation of covalent bonds between proteins and between proteins and polyamines. The aim of the current study was to investigate the time-course of TG hepatic activity in CF1 male mice either acutely or chronically treated with DDC and to correlate this activity with polyamine and porphyrin levels. On day 3 of the treatment, statistically significant increases in TG activity (75%), porphyrin content (6740%) and spermidine levels (73%) were observed. Although not statistically significant, at this time point putrescine levels showed an increase of 52%. The highest TG activity was observed on day 30 (522%), while porphyrin levels were still gradually increasing by day 45 (37,000%). From day 7 of the treatment and until the end of the experiment, putrescine levels remained increased (781%). Spermine levels were not affected by the treatment. The DDC-induced increases in putrescine and spermidine levels herein reported seem to be an early event contributing to the stimulation of liver TG activity, and thus to the promotion of cross-linking reactions between keratin proteins. This in turn would contribute to the formation of protein aggregates, which would lead to the appearance of MDBs. Due to the pro-oxidant and antioxidant properties of polyamines, it is possible to speculate that putrescine and spermidine may also participate at several levels in the oxidative stress processes associated with MDB formation. © 2010 Elsevier Ireland Ltd.
Registro:
Documento: |
Artículo
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Título: | Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model |
Autor: | Cochón, A.C.; Miño, L.A.; San Martín de Viale, L.C. |
Filiación: | Laboratorio de Disturbios Metabólicos Producidos por Xenobióticos, Su Relación con Salud Humana (DIMXSA), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Palabras clave: | 3,5-Diethoxycarbonyl-1,4-dihydrocollidine; Liver; Mallory-Denk bodies.; Polyamine; Porphyrin; Transglutaminase; 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester; keratin; polyamine; porphyrin; protein glutamine gamma glutamyltransferase; putrescine; spermidine; 3,5-diethoxycarbonyl-1,4-dihydrocollidine; polyamine; porphyrin; protein glutamine gamma glutamyltransferase; pyridine derivative; animal experiment; animal model; article; cell inclusion; controlled study; cross linking; disease model; enzyme activity; liver toxicity; male; Mallory Denk body; mouse; nonhuman; oxidative stress; priority journal; protein aggregation; animal; cell inclusion; drug effects; liver; metabolism; toxicity; Animals; Biogenic Polyamines; Inclusion Bodies; Liver; Male; Mice; Models, Animal; Porphyrins; Pyridines; Transglutaminases; Mus; Rodentia; Animals; Biogenic Polyamines; Inclusion Bodies; Liver; Male; Mice; Models, Animal; Porphyrins; Pyridines; Transglutaminases |
Año: | 2010
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Volumen: | 199
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Número: | 2
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Página de inicio: | 160
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Página de fin: | 165
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DOI: |
http://dx.doi.org/10.1016/j.toxlet.2010.08.018 |
Título revista: | Toxicology Letters
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Título revista abreviado: | Toxicol. Lett.
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ISSN: | 03784274
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CODEN: | TOLED
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CAS: | 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester, 12772-36-0, 632-93-9; porphyrin, 24869-67-8; protein glutamine gamma glutamyltransferase, 80146-85-6; putrescine, 110-60-1, 333-93-7; spermidine, 124-20-9, 334-50-9; protein glutamine gamma glutamyltransferase, 80146-85-6; 5-diethoxycarbonyl-1,4-dihydrocollidine; Biogenic Polyamines; Porphyrins; Pyridines; Transglutaminases, 2.3.2.13; 3,5-diethoxycarbonyl-1,4-dihydrocollidine; Biogenic Polyamines; Porphyrins; Pyridines; Transglutaminases
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v199_n2_p160_Cochon |
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Citas:
---------- APA ----------
Cochón, A.C., Miño, L.A. & San Martín de Viale, L.C.
(2010)
. Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model. Toxicology Letters, 199(2), 160-165.
http://dx.doi.org/10.1016/j.toxlet.2010.08.018---------- CHICAGO ----------
Cochón, A.C., Miño, L.A., San Martín de Viale, L.C.
"Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model"
. Toxicology Letters 199, no. 2
(2010) : 160-165.
http://dx.doi.org/10.1016/j.toxlet.2010.08.018---------- MLA ----------
Cochón, A.C., Miño, L.A., San Martín de Viale, L.C.
"Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model"
. Toxicology Letters, vol. 199, no. 2, 2010, pp. 160-165.
http://dx.doi.org/10.1016/j.toxlet.2010.08.018---------- VANCOUVER ----------
Cochón, A.C., Miño, L.A., San Martín de Viale, L.C. Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model. Toxicol. Lett. 2010;199(2):160-165.
http://dx.doi.org/10.1016/j.toxlet.2010.08.018