| Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model. | |
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MedLine Citation:
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PMID: 20832458 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 Ca(2+)-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. |
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Authors:
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Adriana C Cochón; Lelia A Miño; Leonor C San Martín de Viale |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-08 |
Journal Detail:
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Title: Toxicology letters Volume: 199 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-04 Revised Date: 2012-01-27 |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 160-5 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. adcris@qb.fcen.uba.ar |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biogenic Polyamines / analysis* Inclusion Bodies / drug effects, metabolism* Liver / metabolism* Male Mice Models, Animal Porphyrins / analysis Pyridines / toxicity Transglutaminases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/3,5-diethoxycarbonyl-1,4-dihydrocollidine; 0/Biogenic Polyamines; 0/Porphyrins; 0/Pyridines; EC 2.3.2.13/Transglutaminases |
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