Bilirubin secretory pathway and its disorders
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Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This work is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is concerned with the antioxidative properties of...
Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This work is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is concerned with the antioxidative properties of bilirubin in liver tissue in a model of obstructive cholestasis. In the second part we present several novel mutations in ABCC2, the gene associated with Dubin-Johnson syndrome. In the third key study focused on Rotor syndrome we demonstrated that biallelic inactivating mutations causing complete absence of transport proteins OATP1B1 and OATP1B3 result in Rotor-type jaundice. In the last study we confirmed that decreased expression of Rotor proteins may contribute to conjugated hyperbilirubinemia in advanced liver diseases with predominantly obstructive type of cholestasis.
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