Cytoskeletal Disruption Accelerates Caspase-3 Activation and Alters the Intracellular Membrane Reorganization in DNA Damage-Induced Apoptosis

doi:10.1006/excr.2000.4970

Experimental Cell Research

Volume 259, Issue 1, 25 August 2000, Pages 64-78

https://doi.org/10.1006/excr.2000.4970 Get rights and content

Abstract

In actinomycin D (AD)-induced apoptosis, caspase-3 activation and DNA cleavage in human megakaryoblastic leukemia CMK-7 cells were greatly accelerated by tubulin and actin polymerization inhibitors [e.g., colcemid (CL) and cytochalasin D (CD), respectively], but the acceleration was not found with Taxol or phalloidin. A decrease in mitochondrial transmembrane potential, release of cytochrome c into the cytosol, and cleavage of procaspase-9 to its active form preceded the activation of caspase-3 and, moreover, all of these events began earlier and/or proceeded faster in cells treated with AD plus CL or CD than in cells treated with AD only. These results suggest that cytoskeletal disruption in the apoptotic cells promotes damage of the mitochondrial membrane, resulting in the enhanced release of cytochrome c necessary for the activation of caspase-9 that initiates the caspase cascade. On the other hand, apoptotic bodies were rapidly formed from cells treated with AD and CL, but were suppressed when treated with AD and CD. Intracellular membranes and the actin system were reorganized to surround the nuclear fragments in the AD- and CL-treated cells, but such a membrane system was not formed in the presence of CD, implying that the apoptotic bodies are formed via reorganization of intracellular membranes under regulation by actin polymerization. Thus, the cytoskeletal change in CMK-7 cells has a strong effect on the early biochemical process as well as on the later morphologic process in AD-induced apoptosis.

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Regular ArticleCytoskeletal Disruption Accelerates Caspase-3 Activation and Alters the Intracellular Membrane Reorganization in DNA Damage-Induced Apoptosis

Abstract

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Cell

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J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Int. Rev. Cytol.

Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics

Br. J. Cancer

Caspase-3-generated fragment of gelsolin: Effector of morphological change in apoptosis

Science

Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution

Proc. Natl. Acad. Sci. USA

Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis

Cancer Res.

Actin polymerization and depolymerization during apoptosis in HL-60 cells

Am. J. Physiol.

F-actin disorganization in apoptotic cell death of cultured rat renal proximal tubular cells

Am. J. Physiol.

Raf-1/bcl-2 phosphorylation: A step from microtubule damage to cell death

Cancer Res.

Mechanisms of taxol-induced cell death are concentration dependent

Cancer Res.

Microtubule-damaging drugs triggered Bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of Bcl2 protein

Int. J. Oncol.

Temporal relationship of CDK1 activation and mitotic arrest to cytosolic accumulation of cytochrome C and caspase-3 activity during Taxol-induced apoptosis of human AML HL-60 cells

Leukemia

Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase

Mol. Cell. Biol.

Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis

Proc. Natl. Acad. Sci. USA

Regular Article
Cytoskeletal Disruption Accelerates Caspase-3 Activation and Alters the Intracellular Membrane Reorganization in DNA Damage-Induced Apoptosis