Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.696930
Title: The role of ionic K+ in the regulation of apoptosis
Author: Thompson, Gwilym J.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2001
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Abstract:
Cell shrinkage is a major characteristic of apoptotic cell death and is associated with a decrease in intracellular K+ concentration. Intracellular K+ ions have an important role in setting and modulating the plasma membrane potential and can profoundly affect the activity of a number of cellular enzymes. Following initial investigations into the role of K+ in cell survival and apoptosis in primary cultures of cerebellar granule neurons, flux of cellular K+ following induction of apoptosis by death receptor ligation or chemical stress was assessed in Jurkat T cells loaded with the K+ ion surrogate 86Rb+. A time-dependent efflux of intracellular K+ was demonstrated that accompanies cell shrinkage, reduction of mitochondrial transmembrane potential (m) and phosphatidylserine (PS) externalisation. An apparent increase in mitochondrial K+ concentration following treatment of cells with anti-CD95 antibody was also demonstrated. Induction of CD95- or chemical-mediated apoptosis results in depolarisation of the plasma membrane that accompanies PS externalisation and reduction of m. Both depolarisation of the plasma membrane and efflux of intracellular K+ are dependent upon caspase activation in CD95- but not chemical-mediated apoptosis. Consistent with the hypothesis that efflux of intracellular K+ is required for the progression of apoptosis, formation of the caspase-activating ~700 kDa Apaf-1-containing apoptosome complex is inhibited in vitro by 50mM K+. The data imply that K+ plays an important role in the regulation and progression of apoptosis by influencing transmembrane voltage or ion-sensitive enzymatic processes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.696930  DOI: Not available
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