Regulation of BSEP

Transport of bile acids from blood into bile is rate limited by activity of the BSEP, and plays a crucial role both in control of intra-cellular concentrations 

BSEP structure predicts multiple phosphorylation sites, including those for protein kinase C and A (PKC and PKA), within the predicted intra-cellular 

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Figure 15.7 Differences between IL-6- and TNF-a-mediated regulation of hepatobiliary drug transporter expression. IL-6 induces hepatobiliary MRP1 and MRPS expression and leads to downregulation of hepatobiliary MDRl, NTCP, OATP2, and BSEP. Data on its effect on...

BSEP is a liver-specific and ATP-dependent transport protein that mediates the excretion of bile salts into bile and is expressed on the apical plasma membrane domain (canalicular surface) of hepatocytes (Lam et al., 2010). Bile formation and excretion is an essential biological process in higher vertebrates and is an important route of xenobiotic elimination, which also plays a key role in intestinal dissolution and absorption of lipids, vitamins, and fat-soluble food components. Bile salts are synthesized within hepatocytes by cytochrome P450-mediated metabolism of cholesterol and are key components of bile (Hofmann and Hagey, 2008). Bile formation and bile flow are regulated physiologically by complex mechanisms, which in hepatocytes include nuclear hormone receptor-mediated transcriptional pathways and a variety of posttranscriptional processes (Kullak-Ublick et al., 2004 Gonzalez, 2012). 

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