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APOPTOSIS
Article . 2016 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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DIGITAL.CSIC
Article . 2018 . Peer-reviewed
Data sources: DIGITAL.CSIC
APOPTOSIS
Article . 2018
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Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents

Authors: Oropesa-Ávila, Manuel; Cruz, Patricia de la; Porcuna, Jesús; Villanueva-Paz, Marina; Fernández-Vega, Alejandro; Mata, Mario de la; Lavera, I. de; +7 Authors

Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents

Abstract

Cell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase activation and final apoptotic cell morphology. In the one referred as "slow" (~h) or round-shaped, apoptosis was characterized by a slow contraction of the actinomyosin ring and late caspase activation. In "slow" apoptosis the γ-tubulin complexes were not disorganized and microtubules were not depolymerized at early stages. In contrast, "fast" (~min) or irregular-shaped apoptosis was characterized by early caspase activation followed by full contraction of the actinomyosin ring. In fast apoptosis γ-tubulin complexes were disorganized and microtubules were initially depolymerized. However, after actinomyosin contraction, microtubules were reformed adopting a cortical but irregular disposition near plasma membrane. In addition to distinctive cytoskeleton reorganization kinetics, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocytes response. Our results suggest that the knowledge and modulation of the type of apoptosis promoted by genotoxic agents may be important for deciding a better therapeutic option and predicting the immune response in cancer treatment.

Country
Spain
Keywords

Swine, Apoptosis, Microtubules, Phagocytosis, Tubulin, Cell Line, Tumor, Animals, Humans, Cell Shape, Actin, Cytoskeleton, Dose-Response Relationship, Drug, Cell Cycle, Cell Membrane, Actomyosin, Enzyme Activation, Caspases, LLC-PK1 Cells, Camptothecin, Topoisomerase I Inhibitors, actin, DNA Damage

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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10
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