Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency.
J Biol Chem
; 294(31): 11853-11862, 2019 08 02.
Article
en En
| MEDLINE
| ID: mdl-31201272
ABSTRACT
Sodium taurocholate cotransporting polypeptide (NTCP, encoded by Slc10a1/SLC10A1) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in Slc10a1-/- mice, and we also assessed changes of TBA levels in 33 young individuals with SLC10A1 loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both Slc10a1-/- mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic Slc10a1-/- mice, including inhibition of bile acid (BA) synthesis, enhancement of BA detoxification, and altered BA transport. Members of the sulfotransferase (SULT) family showed the most dramatic increases in livers of hypercholanemic Slc10a1-/- mice, and one of their BA sulfates, taurolithocholic acid 3-sulfate, significantly increased. Importantly, consistent with the mouse studies, comprehensive profiling of 58 BA species in sera of p.Ser267Phe individuals revealed a markedly increased level of BA sulfates. Together, our findings indicate that the enhanced BA sulfation is a major mechanism for BA detoxification and elimination in both mice and humans with Slc10a1/SLC10A1 deficiency.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ácido Taurolitocólico
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Ácidos y Sales Biliares
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Transportadores de Anión Orgánico Sodio-Dependiente
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Simportadores
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Biol Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
China