Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized mitochondria

Oropesa, Manuel; Mata, Mario de la; Garrido-Maraver, Juan; Cordero, Mario D.; Cotán, David; Rodríguez-Hernández, Ángeles; Domínguez-Moñino, Irene; Miguel, Manuel de; Navas, Plácido; Sánchez-Alcázar, José Antonio

doi:10.1007/s10495-011-0577-1

Cited by 28 publications

(24 citation statements)

References 45 publications

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“…The amphiphilic nature of PFOS or PFOA suggests that their effects could primarily be associated with the membrane functions. To examine whether more cellular accessibility of PCP is attributed to the membrane effects induced by PFOS (or PFOA), the membrane properties of the cells were evaluated by exposing them to 100 lM PFOS (or PFOA) by FDA and LDH tests, which have been used for evaluating membrane permeability or integrity (Liu et al, 2008;Oropesa et al, 2011). The fluorescence intensity in FDA assay decreased about 18% (or 16%) when the cells were treated with PFOS (or PFOA) compared to the control (Fig.…”

Section: The Mechanism Of Enhanced Cytotoxicity Caused By Addition Ofmentioning

confidence: 99%

Enhanced cytotoxicity of pentachlorophenol by perfluorooctane sulfonate or perfluorooctanoic acid in HepG2 cells

et al. 2013

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h i g h l i g h t sPFOS and PFOA could enhance the cytotoxity of PCP to HepG2 cells. PFOS displayed stronger synergistic cytotoxicity with PCP than PFOA. Cytotoxic enhancement might be via strengthening the phosphorylation uncoupling of PCP. PFOS and PFOA might cause membrane disruption and improve the uptake of PCP. a r t i c l e i n f o t r a c tChlorinated phenols and perfluoroalkyl acids (PFAAs) are two kinds of pollutants which are widely present in the environment. Considering liver is the primary toxic target organ for these two groups of chemicals, it is interesting to evaluate the possible joint effects of them on liver. In this work, the combined toxicity of pentachlorophenol (PCP) and perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) were investigated using HepG2 cells. The results indicated that PFOS and PFOA could strengthen PCP's hepatotoxicity. Further studies showed that rather than intensify the oxidative stress or promote the biotransformation of PCP, PFOS (or PFOA) might lead to strengthening of the oxidative phosphorylation uncoupling of PCP. By measuring the intracellular PCP concentration and the cell membrane properties, it was suggested that PFOS and PFOA could disrupt the plasma membrane and increase the membrane permeability. Thus, more cellular accessibility of PCP was induced when they were co-exposed to PCP and PFOS (or PFOA), leading to increased cytotoxicity. Further research is warranted to better understand the combined toxicity of PFAAs and other environmental pollutants.

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Section: The Mechanism Of Enhanced Cytotoxicity Caused By Addition Ofmentioning

confidence: 99%

Enhanced cytotoxicity of pentachlorophenol by perfluorooctane sulfonate or perfluorooctanoic acid in HepG2 cells

et al. 2013

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“…Thus, in vivo and in vitro experiments have shown that AMN was visualized predominantly in apoptotic cells with polarized/hyperpolarized mitochondria and, on the contrary, was dismantle in apoptotic cells with depolarized mitochondria. These observations suggest that AMN depends on energized mitochondria and high ATP levels [71]. Kinetics examination in pig LLCPK-1α cells expressing GFP-tubulin also showed that AMN was maintained during the execution phase of apoptosis until mitochondria depolarization marked the onset of secondary necrosis.…”

Section: Apoptotic Microtubules Organization and Maintenance Depend Omentioning

confidence: 75%

“…Therefore, it has been proposed that AMN formation depends on the bioenergetic status of apoptotic cells [71].…”

Section: Apoptotic Microtubules Organization and Maintenance Depend Omentioning

confidence: 99%

“…There are forms of cell death which by their nature impair the correct formation of AMN (e.g.mitochondrial toxics and cold exposure) [71] and, as a result, apoptotic cells are not able to maintain plasma membrane integrity. Therefore, apoptotic cell stabilization may provide a new approach for preventing the adverse effects of early secondary necrosis.…”

Section: Zombie Cells: Stabilization Of Apoptotic Cellsmentioning

confidence: 99%

“…The term apoptosis refers to the process of programmed cell death characterized by a stereotypic sequence of cellular events including cell shrinkage, caspase activation and degradation of cell content, blebbing and maintenance of plasma membrane integrity and condensation and fragmentation of DNA, followed by ordered removal by phagocytes [1]. Apoptosis was first described in 1972 as a vital biological phenomenon, with both physiological and pathological implications [2].…”

Section: Introductionmentioning

confidence: 99%

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Cytoskeleton Rearrangements during the Execution Phase of Apoptosis

Doncel¹,

Ojeda²,

Oropesa-Ávila³

et al. 2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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Apoptosis is a regulated energy-dependent process for the elimination of unnecessary or damaged cells during embryonic development, tissue homeostasis and many pathological conditions. Apoptosis is characterized by specific morphological and biochemical features in which caspase activation has a pivotal role. During apoptosis, cells undergo characteristic morphological reorganizations in which the cytoskeleton participates actively. Traditionally, this cytoskeleton rearrangement has been assigned mainly to actinomyosin ring contraction, with microtubule and intermediate filaments both reported to be depolymerized at early stages of apoptosis. However, recent results have shown that microtubules are reformed during the execution phase of apoptosis forming an apoptotic microtubule network (AMN). Current hypothesis proposes that AMN is required to maintain plasma membrane integrity and cell morphology during the execution phase of apoptosis. AMN disruption provokes apoptotic cell collapse, secondary necrosis and the subsequent release of toxic molecules which can damage surrounding cells and promote inflammation. Therefore, AMN formation in physiological or pathological apoptosis is essential for tissue homeostasis.

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Emerging roles of apoptotic microtubules during the execution phase of apoptosis

et al. 2015

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Apoptosis is a genetically programmed energy-dependent process of cell demise, characterized by specific morphological and biochemical events in which the activation of caspases has an essential role. During apoptosis the cytoskeleton participates actively in characteristic morphological rearrangements of the dying cell. This reorganisation has been assigned mainly to actinomyosin ring contraction, while microtubule and intermediate filaments are depolymerized at early stages of apoptosis. However, recent reports have showed that microtubules are reformed during the execution phase of apoptosis organizing an apoptotic microtubule network (AMN). AMN is organized behind plasma membrane, forming a cortical structure. Apoptotic microtubules repolymerization takes place in many cell types and under different apoptotic inducers. It has been hypothesized that AMN is critical for maintaining plasma membrane integrity and cell morphology during the execution phase of apoptosis. AMN disorganization leads apoptotic cells to secondary necrosis and the release of potential toxic molecules which can damage neighbor cells and promotes inflammation. Therefore, AMN formation during physiological apoptosis or in pathological apoptosis induced by anti-cancer treatments is essential for tissue homeostasis and the prevention of additional cell damage and inflammation. V C 2015Wiley Periodicals, Inc.Key Words: apoptosis; microtubules; actin; cytoskeleton Apoptosis A poptosis is an intracellular signaling pathway conserved across evolution dependent on a caspase-mediated proteolytic cascade that leads to a program of cell death through a series of cellular changes distinct of cell necrosis [Kerr et al., 1972]. Apoptosis plays a critical role in tissue remodeling during development, tissue homeostasis, cleaning of senescent cells, and removal of the cells with severe DNA damage [reviewed in Fuchs and Steller, 2011]. Given that cell necrosis causes the release of toxic molecules and causes inflammation [Savill et al., 2002], an important function of apoptosis is to isolate dying cells and prepare them for elimination by phagocytosis. This program of cell death is carried out by organelle-directed regulators, including the Bcl-2 proteins [Czabotar et al., 2014], and ultimately executed by cysteine proteases of the caspase family [Aslan and Thomas, 2009;McIlwain et al., 2015]. Some caspases, such caspase-8 and 29, operate as "initiators" and transmit cell-death signals by activating "executioner or effector" caspases, such as caspase-3, 26 and 27. After activation, "effector" caspases cleave a wide range of cellular proteins that are required for cell survival [Poreba et al., 2013]. Caspase activation can be initiated by extracellular stimuli as well as by alterations of intracellular homeostasis that often converge primarily or secondarily at mitochondria [Tait and Green, 2010]. Regardless of the precise molecular mechanisms leading to caspase activation, apoptotic cells exhibit characteristic features, eventually fragmenting into discre...

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Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized mitochondria

Cited by 28 publications

References 45 publications

Enhanced cytotoxicity of pentachlorophenol by perfluorooctane sulfonate or perfluorooctanoic acid in HepG2 cells

Enhanced cytotoxicity of pentachlorophenol by perfluorooctane sulfonate or perfluorooctanoic acid in HepG2 cells

Cytoskeleton Rearrangements during the Execution Phase of Apoptosis

Emerging roles of apoptotic microtubules during the execution phase of apoptosis

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