Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model

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...

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Autores principales:	Cochón, Adriana Cristina, San Martín de Viale, Leonor Carmen
Publicado:	2010
Materias:	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 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 drug effects liver metabolism toxicity Animals Biogenic Polyamines Inclusion Bodies Male Mice Models, Animal Porphyrins Pyridines Transglutaminases Mus Rodentia
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v199_n2_p160_Cochon http://hdl.handle.net/20.500.12110/paper_03784274_v199_n2_p160_Cochon
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_03784274_v199_n2_p160_Cochon
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spelling	paper:paper_03784274_v199_n2_p160_Cochon2023-06-08T15:39:43Z Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model Cochón, Adriana Cristina San Martín de Viale, Leonor Carmen 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 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. Fil:Cochón, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v199_n2_p160_Cochon http://hdl.handle.net/20.500.12110/paper_03784274_v199_n2_p160_Cochon
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Cochón, Adriana Cristina San Martín de Viale, Leonor Carmen Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
topic_facet	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
description	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.
author	Cochón, Adriana Cristina San Martín de Viale, Leonor Carmen
author_facet	Cochón, Adriana Cristina San Martín de Viale, Leonor Carmen
author_sort	Cochón, Adriana Cristina
title	Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
title_short	Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
title_full	Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
title_fullStr	Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
title_full_unstemmed	Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model
title_sort	early increases in transglutaminase activity and polyamine levels in a mallory-denk body mouse model
publishDate	2010
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v199_n2_p160_Cochon http://hdl.handle.net/20.500.12110/paper_03784274_v199_n2_p160_Cochon
work_keys_str_mv	AT cochonadrianacristina earlyincreasesintransglutaminaseactivityandpolyaminelevelsinamallorydenkbodymousemodel AT sanmartindevialeleonorcarmen earlyincreasesintransglutaminaseactivityandpolyaminelevelsinamallorydenkbodymousemodel
_version_	1768542792159592448

Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model

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