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Bile Proteome in Health and Disease

Annarita Farina, Myriam Delhaye, Pierre Lescuyer, Jean‐Marc Dumonceau

10.1002/cphy.c130016

Source: Volume 4, Issue 1, January 2014

Published online: January 2014

Full Article on Wiley Online Library



Abstract

The study of bile proteins could improve the understanding of physiological processes involved in the regulation of the hepato‐biliary system. Researchers have tried for years to investigate the bile proteome but, until recently, only a few tens of proteins were known. The advent of proteomics, availing of large‐scale analytical devices paired with potent bioinformatic resources, lately allowed the identification of thousands of proteins in bile. Nevertheless, the knowledge of their role in the hepato‐biliary system still represents almost a “blank page in the book of physiology.” In this review, we first guide the reader through the historical phases of the analysis of bile protein content, emphasizing the recent progresses achieved through the use of proteomic techniques. Thereafter, we deeply explore the involvement of bile proteins in health and disease, with a particular focus on the discovery of biomarkers for biliary tract malignancies. © 2014 American Physiological Society. Compr Physiol 4:91‐108, 2014.

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Figure 1. Figure 1. Composition of hepatic and gallbladder bile (adapted from Ref. 55, with the permission of Elsevier).
Figure 2. Figure 2. Tissue specificity analysis of the complete catalogue of bile proteins.
Figure 3. Figure 3. Release mechanisms of proteins in bile. Release mechanisms of proteins in bile. (A) Paracellular pathway. Proteins enter bile canaliculi through tight junctions between adjacent hepatocytes. Low‐molecular weight proteins are favored. (B) Transcellular pathway, nonspecific endocytotic route. Proteins are first internalized by hepatocytes and then released into canaliculi. No discrimination is shown between low and high molecular weight proteins. Vesicles directly transferred to the canalicular membrane release proteins in their intact form (b1), while vesicles which fuse with lysosomes discharge protein fragments resulting from enzymatic digestion (b2). (C) Transcellular pathway, specific endocytotic route. The vesicular uptake of proteins is carried out through specific membrane receptors. Lysosomal (c2) and nonlysosomal (c1) endocytotic routes exist. In some cases, intact proteins linked to a proteolyzed fragment of their receptor may be released (c1).


Figure 1. Composition of hepatic and gallbladder bile (adapted from Ref. 55, with the permission of Elsevier).


Figure 2. Tissue specificity analysis of the complete catalogue of bile proteins.


Figure 3. Release mechanisms of proteins in bile. Release mechanisms of proteins in bile. (A) Paracellular pathway. Proteins enter bile canaliculi through tight junctions between adjacent hepatocytes. Low‐molecular weight proteins are favored. (B) Transcellular pathway, nonspecific endocytotic route. Proteins are first internalized by hepatocytes and then released into canaliculi. No discrimination is shown between low and high molecular weight proteins. Vesicles directly transferred to the canalicular membrane release proteins in their intact form (b1), while vesicles which fuse with lysosomes discharge protein fragments resulting from enzymatic digestion (b2). (C) Transcellular pathway, specific endocytotic route. The vesicular uptake of proteins is carried out through specific membrane receptors. Lysosomal (c2) and nonlysosomal (c1) endocytotic routes exist. In some cases, intact proteins linked to a proteolyzed fragment of their receptor may be released (c1).
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Supplementary Information

Supplementary Table I: Comprehensive catalogue of gene products described to date in human bile by using proteomic approaches. Download (xlsx)

Supplementary Table II: List of bile proteins categorized in functional and biological classes. Download (pdf)

Supplementary Figure I: Characterization of the complete catalogue of bile proteins in terms of molecular functions. Highly enriched categories are shown in red. Download (bmp) Download (gif)

Supplementary Figure II: Characterization of the complete catalogue of bile proteins in terms of biological processes. Highly enriched categories are shown in red. Download (bmp) Download (gif)


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Article Title: Bile Proteome in Health and Disease
 

How to Cite

Annarita Farina, Myriam Delhaye, Pierre Lescuyer, Jean‐Marc Dumonceau. Bile Proteome in Health and Disease. Compr Physiol 2014, 4: 91-108. doi: 10.1002/cphy.c130016