Publication

Functional regulation of transport proteins in gastrointestinal and liver disease

Blokzijl, J., 2008, [S.n.]. 179 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Johannes Blokzijl
The liver and intestine have an important role in the metabolism of the human body. Nutrients are absorbed and digested in the intestine and subsequently taken up by the blood and transported tot the liver. The liver is responsible for the metabolism of carbohydrates, proteins and hormones and the formation of bile. The hepatocyt has highly specialized transport proteins located at the basolateral (sinusoidal) and canalicular (apical) membrane for the uptake and excretion of dietary compounds, bile constituents and xenotoxins. Members of the ATP binding cassette (ABC) transporter family have an important role in transport of these substrates and are able to transport these across the cell membrane against a concentration gradient. Recently, it has become clear that nuclear receptors (NRs) play an important role in the transcriptional regulations of transporter genes. NR are transcription factors that are activated by specific ligands. Binding of a ligand leads to conformational changes and recruitment/dissociation of cofactors, which increases the binding affinity to specific DNA sequences in promoter elements of a subset of genes. This mechanism may lead to either induction or repression of the NR-target gene. Many of the ligands of NRs are substrates for ABC-transporters, thereby creating a regulatory loop for maintaining optimal cellular levels of these compounds. This discovery has led to an increased understanding of the molecular mechanisms that are involved in the development of decreased bile flow (cholestasis).
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date15-Oct-2008
Publisher
Print ISBNs9789071382482
Publication statusPublished - 2008

    Keywords

  • Transporteiwitten, Maagdarmziekten, Leverziekten, Proefschriften (vorm), gastro-enterologie

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