Document Detail


Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey.
MedLine Citation:
PMID:  22733776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bile salt synthesis is a specialized liver function in vertebrates. Bile salts play diverse roles in digestion and signaling, and their homeostasis is maintained by controlling input (biosynthesis) and intestinal conservation. Patients with biliary atresia (i.e., obliteration of the biliary tree) suffer liver fibrosis and cirrhosis. In contrast, sea lamprey thrives despite developmental biliary atresia. We discovered that the sea lamprey adapts to biliary atresia through a unique mechanism of de novo synthesis and secretion of bile salts in intestine after developmental biliary atresia, in addition to known mechanisms, such as the reduction of bile salt synthesis in liver. During and after developmental biliary atresia, expression of cyp7a1 in intestine increased by more than 100-fold (P < 0.001), whereas in liver it decreased by the same magnitude (P < 0.001). Concurrently, bile salt pools changed in similar patterns and magnitudes in these two organs and the composition shifted from C24 bile alcohol sulfates to taurine-conjugated C24 bile acids. In addition, both in vivo and ex vivo experiments showed that aductular sea lamprey secreted taurocholic acid into its intestinal lumen. Our results indicate that the sea lamprey, a jawless vertebrate, may be in an evolutionarily transitional state where bile salt synthesis occurs in both liver and intestine. Understanding the molecular basis of these mechanisms may shed light on the evolution of bile salt synthesis and possible therapy for infant biliary atresia.
Authors:
Chu-Yin Yeh; Yu-Wen Chung-Davidson; Huiyong Wang; Ke Li; Weiming Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-06-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-11     Completed Date:  2012-10-05     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11419-24     Citation Subset:  IM    
Affiliation:
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile Acids and Salts / chemistry*
Biliary Atresia / metabolism*
Cholestasis
Cholesterol 7-alpha-Hydroxylase / metabolism
Chromatography, Liquid / methods
Chromatography, Thin Layer / methods
Fibrosis / pathology
Intestines / metabolism
Liver / metabolism,  pathology
Mass Spectrometry / methods
Mucous Membrane / metabolism
Perfusion
Petromyzon / physiology*
Polymerase Chain Reaction / methods
Taurine / chemistry
Grant Support
ID/Acronym/Agency:
5R24GM83982/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 107-35-7/Taurine; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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