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Jochen HM Prehn
D Kögel
A L Nieminen
D Böckelmann
C M Luetjens
A J Krohn
H Düssmann
C Reimertz
M Poppe



staurosporine inbred f344 bcl x protein physics ionophores rats inbred f344 neurons protons mitochondria rats physiology potassium caspase 3 immunohistochemistry fluorescent dyes proto oncogene proteins c bcl 2 medulloblastoma apoptosis animals transfection cells cultured enzyme inhibitors cells valinomycin caspases hippocampus cultured cytochrome c group

Dissipation of potassium and proton gradients inhibits mitochondrial hyperpolarization and cytochrome c release during neural apoptosis. (2001)

Abstract Exposure of rat hippocampal neurons or human D283 medulloblastoma cells to the apoptosis-inducing kinase inhibitor staurosporine induced rapid cytochrome c release from mitochondria and activation of the executioner caspase-3. Measurements of cellular tetramethylrhodamine ethyl ester fluorescence and subsequent simulation of fluorescence changes based on Nernst calculations of fluorescence in the extracellular, cytoplasmic, and mitochondrial compartments revealed that the release of cytochrome c was preceded by mitochondrial hyperpolarization. Overexpression of the anti-apoptotic protein Bcl-xL, but not pharmacological blockade of outward potassium currents, inhibited staurosporine-induced hyperpolarization and apoptosis. Dissipation of mitochondrial potassium and proton gradients by valinomycin or carbonyl cyanide p-trifluoromethoxy-phenylhydrazone also potently inhibited staurosporine-induced hyperpolarization, cytochrome c release, and caspase activation. This effect was not attributable to changes in cellular ATP levels. Prolonged exposure to valinomycin induced significant matrix swelling, and per se also caused release of cytochrome c from mitochondria. In contrast to staurosporine, however, valinomycin-induced cytochrome c release and cell death were not associated with caspase-3 activation and insensitive to Bcl-xL overexpression. Our data suggest two distinct mechanisms for mitochondrial cytochrome c release: (1) active cytochrome c release associated with early mitochondrial hyperpolarization, leading to neuronal apoptosis, and (2) passive cytochrome c release secondary to mitochondrial depolarization and matrix swelling.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, D Kögel, A L Nieminen, D Böckelmann, C M Luetjens, A J Krohn, H Düssmann, C Reimertz, M Poppe

Experts in our system

Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Donat Kögel
Royal College of Surgeons in Ireland
Total Publications: 14
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45