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Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis

We investigated the effects of obstructive cholestasis in different hepatic lobes by evaluating asymmetric dimethylarginine (ADMA) (a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (enzymes involved, resp., in its synthesis and d...

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Autores principales: Ferrigno, Andrea, Palladini, Giuseppina, Bianchi, Alberto, Rizzo, Vittoria, Di Pasqua, Laura G., Perlini, Stefano, Richelmi, Plinio, Vairetti, Mariapia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075188/
https://www.ncbi.nlm.nih.gov/pubmed/25013773
http://dx.doi.org/10.1155/2014/327537
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author Ferrigno, Andrea
Palladini, Giuseppina
Bianchi, Alberto
Rizzo, Vittoria
Di Pasqua, Laura G.
Perlini, Stefano
Richelmi, Plinio
Vairetti, Mariapia
author_facet Ferrigno, Andrea
Palladini, Giuseppina
Bianchi, Alberto
Rizzo, Vittoria
Di Pasqua, Laura G.
Perlini, Stefano
Richelmi, Plinio
Vairetti, Mariapia
author_sort Ferrigno, Andrea
collection PubMed
description We investigated the effects of obstructive cholestasis in different hepatic lobes by evaluating asymmetric dimethylarginine (ADMA) (a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (enzymes involved, resp., in its synthesis and degradation), the cationic transporter (CAT), and metalloproteinase (MMP) activity. Sixteen male Wistar rats underwent a 3-day cholestasis by common bile duct ligation (BDL) or sham operation. Blood samples and hepatic biopsies from left lobe (LL), median lobe (ML), and right lobe (RL) were collected. Serum hepatic enzymes, tissue ADMA, DDAH activity, CAT-2 protein, mRNA expression of DDAH and PRMT, and MMP-2 and MMP-9 activity were monitored. Cholestasis was confirmed by altered serum hepatic enzymes. Higher levels of tissue ADMA were detected in RL and ML as compared with LL. PRMT mRNA expression and DDAH activity did not differ among the lobes after BDL. CAT-2 levels are higher in the RL and ML in the sham-operated group. Higher activity in MMP-2 and MMP-9 was found in RL. In conclusion, after cholestasis an increase in hepatic ADMA in RL and ML was detected as well as tissue MMP-2 and MMP-9 activation in RL, supporting the evidence of functional heterogeneity among the liver lobes also occurring in an obstructive cholestasis model.
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spelling pubmed-40751882014-07-10 Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis Ferrigno, Andrea Palladini, Giuseppina Bianchi, Alberto Rizzo, Vittoria Di Pasqua, Laura G. Perlini, Stefano Richelmi, Plinio Vairetti, Mariapia Biomed Res Int Research Article We investigated the effects of obstructive cholestasis in different hepatic lobes by evaluating asymmetric dimethylarginine (ADMA) (a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (enzymes involved, resp., in its synthesis and degradation), the cationic transporter (CAT), and metalloproteinase (MMP) activity. Sixteen male Wistar rats underwent a 3-day cholestasis by common bile duct ligation (BDL) or sham operation. Blood samples and hepatic biopsies from left lobe (LL), median lobe (ML), and right lobe (RL) were collected. Serum hepatic enzymes, tissue ADMA, DDAH activity, CAT-2 protein, mRNA expression of DDAH and PRMT, and MMP-2 and MMP-9 activity were monitored. Cholestasis was confirmed by altered serum hepatic enzymes. Higher levels of tissue ADMA were detected in RL and ML as compared with LL. PRMT mRNA expression and DDAH activity did not differ among the lobes after BDL. CAT-2 levels are higher in the RL and ML in the sham-operated group. Higher activity in MMP-2 and MMP-9 was found in RL. In conclusion, after cholestasis an increase in hepatic ADMA in RL and ML was detected as well as tissue MMP-2 and MMP-9 activation in RL, supporting the evidence of functional heterogeneity among the liver lobes also occurring in an obstructive cholestasis model. Hindawi Publishing Corporation 2014 2014-06-12 /pmc/articles/PMC4075188/ /pubmed/25013773 http://dx.doi.org/10.1155/2014/327537 Text en Copyright © 2014 Andrea Ferrigno et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ferrigno, Andrea
Palladini, Giuseppina
Bianchi, Alberto
Rizzo, Vittoria
Di Pasqua, Laura G.
Perlini, Stefano
Richelmi, Plinio
Vairetti, Mariapia
Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title_full Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title_fullStr Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title_full_unstemmed Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title_short Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis
title_sort lobe-specific heterogeneity in asymmetric dimethylarginine and matrix metalloproteinase levels in a rat model of obstructive cholestasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075188/
https://www.ncbi.nlm.nih.gov/pubmed/25013773
http://dx.doi.org/10.1155/2014/327537
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