Apoptosis is a distinct form of cell death, which requires energy. Here, we made real-time continuous measurements of the cytosolic ATP level throughout the apoptotic process in intact HeLa, PC12 and U937 cells transfected with the firefly luciferase gene. Apoptotic stimuli (staurosporine (STS), tumor necrosis factor a (TNFa), etoposide) induced significant elevation of the cytosolic ATP level. The cytosolic ATP level remained at a higher level than in the control for up to 6 h during which activation of caspase-3 and internucleosomal DNA fragmentation took place. When the STS-induced ATP response was abolished by glucose deprivation-induced inhibition of glycolysis, both caspase activation and DNA laddering were completely inhibited. Annexin V-binding induced by STS or TNFa was largely suppressed by glycolysis inhibition. Thus, it is suggested that the cells die with increased cytosolic ATP, and elevation of cytosolic ATP level is a requisite to the apoptotic cell death process.
Five sesquiterpene alcohol esters of the carotane series, from plants of the genus Ferula, were investigated with regard to their capacity to modify the ion permeability of both planar lipid bilayers and mitochondria. These compounds are subdivided into two structural groups that differ in their effects on membrane permeability. Complex esters of sesquiterpene alcohols with aliphatic acids, which constituted the first group (lapidin and lapiferin), do not possess ionophoric properties. The second group comprised complex esters of sesquiterpene alcohols with aromatic acids (ferutinin, tenuferidin and ferutidin), all of which increase cation permeability of lipid bilayers and mitochondria in a dose-dependent manner. A pronounced selectivity of the terpenoid-modified membranes for divalent cations versus monovalent cations was found. Evidence of a carrier mechanism for terpenoid-induced ion transport is demonstrated. A tentative complex composed of a divalent cation with two molecules of membrane-active terpenoid is proposed.
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