Signal transduction pathways in hepatocyte cell death. New targets for therapy
PhD ceremony: Ms. G. Karimian, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Signal transduction pathways in hepatocyte cell death. New targets for therapy
Promotor(s): prof. A.J. Moshage, prof. K.N. Faber
Faculty: Medical Sciences
Cholestatic and steatotic liver diseases comprise a significant share of the total burden of chronic liver diseases. Both diseases are associated with a high morbidity and mortality. Existing therapeutic agents are either not very effective or are associated with severe difficulties. Both groups of diseases are characterized by a gradual and progressive loss of viable hepatocytes leading to liver inflammation, fibrogenesis and end-stage liver disease. Hepatocyte cell death can occur via either apoptosis or necrosis (or intermediate forms). Knowledge about the cellular mechanisms regulating death and survival of liver cells is of clinical and scientific interest for developing new therapeutic strategies. The aim of this thesis is to elucidate the mechanisms of cell death in hepatocytes, in order to develop strategies to protect hepatocytes and prevent liver injury.
Three models of hepatocyte cell death were studied: glycochenodeoxycholic acid (GCDCA)-induced cell death as a model for bile acid toxicity, tumor necrosis factor α (TNFα)/ actinomycin D (ActD, an inhibitor of transcription) as a model for cytokine-induced toxicity and menadione-induced cell death (menadione is a superoxide anion donor) as a model for oxidative stress-induced toxicity. These models are clinically relevant as these toxic stimuli are present at increased levels in most liver diseases. This thesis describes that hepatocyte death and survival are regulated at the cross-roads of intracellular organelles (e.g., mitochondria and endoplasmic reticulum), membrane-bound receptors (such as GPCRs and EGFR) and cell survival signaling pathways (such as ERK, PI3K and PKC).
Last modified: | 13 March 2020 12.59 a.m. |
More news
-
02 July 2025
Relinde Weil reappointed as a member of the Supervisory Board UG
The Minister of Education has reappointed Relinde Weil for a second term as a member of the Supervisory Board of the University of Groningen.
-
01 July 2025
Khalaf Alkhalaf elected Alumnus of the Year 2025
Khalaf Alkhalaf has been elected Alumnus of the Year 2025 by the University of Groningen. He has received the award for his commitment to providing good care and guidance to refugees in the Netherlands and the inspiring way in which he shares his...