Mitochondrial hepatopathies: Advances in genetics and pathogenesis

Way S. Lee, Ronald J. Sokol – 30 May 2007 – Hepatic involvement is a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period. Respiratory chain disorders may present as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. In recent years, specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and the deletion or rearrangement of mitochondrial DNA) have been identified, with the promise of genetic and prenatal diagnosis.

4‐phenylbutyrate enhances the cell surface expression and the transport capacity of wild‐type and mutated bile salt export pumps

Hisamitsu Hayashi, Yuichi Sugiyama – 30 May 2007 – Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a mutation in the bile salt export pump (BSEP/ABCB11) gene. We previously reported that E297G and D482G BSEP, which are frequently found mutations in European patients, result in impaired membrane trafficking, whereas both mutants retain their transport function. The dysfunctional localization is probably attributable to the retention of BSEP in endoplasmic reticulum (ER) followed by proteasomal degradation.

Tissue‐type plasminogen activator deficiency exacerbates cholestatic liver injury in mice

Hongtao Wang, Yan Zhang, Robert O. Heuckeroth – 30 May 2007 – Recent studies demonstrating a role for plasminogen activator inhibitor (PAI)‐1 in cholestatic liver disease in mice suggested that tissue‐type plasminogen activator (tPA) or urokinase plasminogen activator (uPA) might be important after biliary tract obstruction. We now demonstrate that blocking tPA exacerbates liver injury after bile duct ligation (BDL).

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