Caspase-3 activation during the process of apoptosis induced by a vacuolar type H(+)-ATPase inhibitor.
Concanamycin A, a specific inhibitor of vacuolar type H(+)-ATPases, induced DNA fragmentation in B cell hybridoma HS-72 cells. Immunoblot analysis revealed that the exposure of concanamycin A to HS-72 cells induced the cleavage of retinoblastoma protein (Rb) and poly(ADP-ribose) polymerase (PARP). The cytosol from concanamycin A-treated HS-72 cells induced DNA fragmentation in nuclei from untreated cells in a cell-free system. This fragmentation was suppressed by a specific inhibitor of caspase-3. The cytosol induced Rb proteolysis in vitro, which was inhibited by a caspase-3 inhibitor. These findings indicate that caspase-3 induces DNA fragmentation and cleavage of Rb and PARP during the process of apoptosis induced by concanamycin A.
Ishisaki
A
A
Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan.
Hashimoto
S
S
Amagasa
T
T
Nishihara
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D020170:Caspase 1 / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006825:Hybridomas / Q000502:physiology; D015151:Immunoblotting; D018942:Macrolides; D051379:Mice; D008856:Microscopy, Fluorescence; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D025262:Vacuolar Proton-Translocating ATPases
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D011506:Proteins; D016160:Retinoblastoma Protein; C036978:concanamycin A; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases