Modification of physicochemical properties of actin filaments suppresses cell fragmentation in the execution phase of staurosporine-induced apoptotic processes.
Effects of jasplakinolide (JSP), a stabilizer of F-actin, and latrunculin A (LTA), a destabilizer of F-actin, on a series of events occurring in the execution phase of staurosporine (STS)-induced apoptotic processes were studied using human osteosarcoma 143B cells. Time-dependent apparent increases of the population of cells with collapsed membrane potential of mitochondria (Delta Psi(m)) caused by STS treatment were not due to actual decreases in the Delta Psi(m) per cell, but due to the fragmentation of cells resulting in decreases in the number of active mitochondria per cell. Decreases in the Delta Psi(m) in fragmented cells occurred late in the execution phase. Both JSP and LAT failed to prevent STS-induced release of cytochrome c from mitochondria followed by the activation of caspases 3 and 9, the cleavage of poly (ADP-ribose) polymerase (PARP) and apoptotic nuclear fragmentation. However, both drugs prevented STS-induced apoptotic cell fragmentation and decreases in the Delta Psi(m). These results indicate that physicochemical states of actin filaments play a certain role in the execution phase of STS-induced apoptotic processes.
Majczak
Anna
A
Department of Cell Biology and Molecular Pathology, Medical University of Gdańsk, ul. Debinki 1, 80-210 Gdańsk, Poland.
Karbowski
Mariusz
M
Kamiński
Marcin
M
Masaoka
Makoto
M
Kurono
Chieko
C
Niemczyk
Edyta
E
Kedzior
Jakub
J
Soji
Tsuyoshi
T
Knap
Dorota
D
Hallmann
Anna
A
Wakabayashi
Takashi
T
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D019311:Staurosporine / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; D020169:Caspases; D019311:Staurosporine; C037067:latrunculin A