[PMID]: | 29346429 |
[Au] Autor: | Ferrigno A; Di Pasqua LG; Berardo C; Siciliano V; Rizzo V; Adorini L; Richelmi P; Vairetti M |
[Ad] Endereço: | Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. |
[Ti] Título: | The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion injury. |
[So] Source: | PLoS One;13(1):e0191430, 2018. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated. After a 60 min reperfusion, serum, tissue and bile ADMA levels, liver mRNA and protein expression of ADMA transporters (CAT-1, CAT-2A, CAT-2B, OCT-1, MATE-1), and enzymes involved in ADMA synthesis (protein-arginine-N-methyltransferase-1, PRMT-1) and metabolism (dimethylarginine-dimethylaminohydrolase-1, DDAH-1) were measured. RESULTS: OCA administration induced a further increase in biliary ADMA levels both in sham and I/R groups, with no significant changes in hepatic ADMA content. A reduction in CAT-1, CAT-2A or CAT-2B transcripts was found in OCA-treated sham-operated rats compared with vehicle. Conversely, OCA administration did not change CAT-1, CAT-2A or CAT-2B expression, already reduced by I/R. However, a marked decrease in OCT-1 and increase in MATE-1 expression was observed. A similar trend occurred with protein expression. CONCLUSION: The reduced mRNA expression of hepatic CAT transporters suggests that the increase in serum ADMA levels is probably due to decreased liver uptake of ADMA from the systemic circulation. Conversely, the mechanism involved in further increasing biliary ADMA levels in sham and I/R groups treated with OCA appears to be MATE-1-dependent. |
[Mh] Termos MeSH primário: |
Antiporters/metabolismo Arginina/análogos & derivados Sistema Biliar/efeitos dos fármacos Ácido Quenodesoxicólico/análogos & derivados Hepatopatias/metabolismo Proteínas de Transporte de Cátions Orgânicos/metabolismo Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores Traumatismo por Reperfusão/metabolismo Regulação para Cima/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Animais Arginina/sangue Arginina/metabolismo Arginina/secreção Sistema Biliar/metabolismo Sistema Biliar/secreção Western Blotting Proteínas de Transporte/genética Proteínas de Transporte/metabolismo Ácido Quenodesoxicólico/farmacologia Masculino Óxido Nítrico Sintase/metabolismo Proteína-Arginina N-Metiltransferases/genética RNA Mensageiro/genética Ratos Ratos Wistar Reação em Cadeia da Polimerase em Tempo Real
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Antiporters); 0 (Carrier Proteins); 0 (MATE1 protein, rat); 0 (Organic Cation Transport Proteins); 0 (RNA, Messenger); 0 (Receptors, Cytoplasmic and Nuclear); 0 (farnesoid X-activated receptor); 0462Z4S4OZ (obeticholic acid); 0GEI24LG0J (Chenodeoxycholic Acid); 63CV1GEK3Y (N,N-dimethylarginine); 94ZLA3W45F (Arginine); EC 1.14.13.39 (Nitric Oxide Synthase); EC 2.1.1.319 (PRMT1 protein, rat); EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) |
[Em] Mês de entrada: | 1803 |
[Cu] Atualização por classe: | 180309 |
[Lr] Data última revisão:
| 180309 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180119 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0191430 |
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