Pro-apoptotic function of checkpoint kinase-2 in syncytia elicited by the HIV-1 envelope

Séror, Claire; Raza, Syed Qasim; Brottes, F; Subra, Frédéric; Piacentini, Mauro; Perfettini, Jean-Luc; Kroemer, Guido

doi:10.4161/cc.8.3.7642

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…The presence of multiple disseminated foci composed of microglia, macrophages and multinucleated giant cells is a hallmark of complex dementia in adults [5,30]. However, we did not find multinucleated giant cells in the samples of any children with HIV-EP included in the study.…”

Section: Discussioncontrasting

confidence: 62%

Different profiles of apoptosis and activation in children with progressive or static HIV-related encephalopathy

Blanco

Nardacci

Nonno

et al. 2015

J Pediatr Infect Dis

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To analyze neurodegeneration in brain cortex samples from human immunodeficiency virus (HIV)-vertically-infected children diagnosed with progressive or static HIV-encephalopathy. We performed a descriptive retrospective and cross-sectional study on 15 HIV-infected children. Eight children were diagnosed with progressive-encephalopathy (EP) and seven with static-EP. Autopsy samples of the frontal cortex from the 15 children were studied. Apoptotic analysis was performed by an assay, which detects apoptotic cells by labeling the fragmentation of DNA by TdT -mediated dUTP nick end labeling (TUNEL) assay. The presence of phosphorylated p53 (p53Ser46P) indicates the beginning of the cell death process. Glial fibrillary acidic protein a marker for glial cells, and p53Ser46P were detected by immunohistochemical assays. All samples from the 15 HIV-infected children showed positive results using TUNEL and showed an increase in p53Ser46P. However, the number of apoptotic cells was higher in samples from children with progressive-EP and was comprised of a higher number of dying neurons than dying glial cells. In contrast, glial cells were more affected in children with static-EP. We observed gliosis (abnormal proliferation of astrocytes in damaged areas of the brain) in all samples, but in the static-EP samples, gliosis was observed in areas close to blood vessels, and it was more pronounced than in progressive-EP samples. Our results suggest that depending whether the diagnosis is progressive-EP or static-EP, neural affliction activates programmed cell death in brain tissue of HIV-infected children. Moreover, there are differences in the type of cellular population affected as well as in the level of glial cell activation.

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Section: Discussioncontrasting

confidence: 62%

Different profiles of apoptosis and activation in children with progressive or static HIV-related encephalopathy

Blanco

Nardacci

Nonno

et al. 2015

J Pediatr Infect Dis

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“…33 Similarly, depletion of Chk1 accelerates the spontaneous apoptosis of polyploid cells resulting from aberrant cell fusion. 35 We also found that the knockdown of endonuclease G killed tetraploid colon cancer cells, a result that could be recapitulated by eliminating endonuclease G from the genome of tetraploid yeast cells. 36 at 30-40% confluence by means of the HiPerFect transfection reagent (Qiagen, Hilden, Germany) as previously described.…”

Section: Resultsmentioning

confidence: 80%

Preferential killing of tetraploid tumor cells by targeting the mitotic kinesin Eg5

Rello-Varona

Vitale²,

Kepp

et al. 2009

Cell Cycle

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Tetraploid cells may constitute a metastable intermediate between normal euploidy and cancer-associated aneuploidy.Tetraploid cells are relatively more resistant against DNA damaging agents and are genetically unstable, due to their tendency towards multipolar, asymmetric division. Therefore, it is important to develop strategies for the selective removal of tetraploid cells. Here, we show that targeting the mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP) by a small interfering RNA (siRNA) or by the pharmacological inhibitor dimethylenastron (DIMEN) kills tetraploid tumor cells more efficiently than their diploid precursors. Cell death occurs after an attempt of monoastral mitosis that, in diploid cells, is followed by a prolonged mitotic arrest and morphological reversion to the interphase, with a 4n DNA content. In contrast, DIMEN-treated tetraploid cells exhibit a shorter mitotic arrest, bipolar or multipolar karyokinesis, followed by apoptosis of the daughter cells, as assessed by fluorescence videomicroscopy of cells that express a histone 2B-GFP fusion construct to monitor their chromosomes. Cell death occurred with hallmarks of apoptosis, namely loss of the mitochondrial transmembrane potential and terminal chromatin compaction. In conclusion, tetraploid cells are particular vulnerable to undergo mitotic catastrophe after genetic or pharmacological inhibition of Eg5.

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“…10 Thus, the inhibition of Chk1 was shown to kill tetraploid cells through a pathway that involves the p38 MAPK -dependent activation of p53, 11 followed by p53-dependent activation of Bax-/Bak-dependent mitochondrial outer membrane permeabilization (MOMP). [12][13][14][15] Because the aforementioned results were obtained in transformed cells, they cannot be extrapolated to the physiology of Report p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis primary non-transformed cells, in which the suppression of tetraploidy ensured by apoptosis might constitute a barrier against oncogenesis. Therefore, we decided to reinvestigate the contribution of p53 and apoptosis to the inhibition of tetraploidization in primary epithelial cells from the mammary gland.…”

Section: Introductionmentioning

confidence: 99%

p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis

Senovilla

Vitale²,

Galluzzi

et al. 2009

Cell Cycle

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Tetraploidy may constitute a metastable state leading to numeric and structural chromosome abnormalities that are associated with cancer. Here, we show that cultured primary p53 -/-(but not wild type, WT) mouse mammary epithelial cells (MMECs) accumulate a tetraploid sub-population in vitro. This occurs spontaneously, yet can be exacerbated by the addition of microtubule inhibitors as well as of inhibitors of cytokinesis. As compared to WT cells, tetraploid p53 -/-MMECs contain supernumerary centrosomes and exhibit a reduced propensity to initiate the mitochondrial pathway of apoptosis. Moreover, tetraploid p53 -/-MMECs are more resistant against anthracyclininduced cell killing than their diploid counterparts. Altogether, these data indicate that p53 normally suppresses the generation of tetraploid cells, presumably by activating the intrinsic pathway of apoptosis. In the absence of p53, tetraploid cells accumulate as a result of inhibited apoptosis, which contributes to the acquisition of chemotherapy resistance.

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Pro-apoptotic function of checkpoint kinase-2 in syncytia elicited by the HIV-1 envelope

Cited by 7 publications

References 39 publications

Different profiles of apoptosis and activation in children with progressive or static HIV-related encephalopathy

Different profiles of apoptosis and activation in children with progressive or static HIV-related encephalopathy

Preferential killing of tetraploid tumor cells by targeting the mitotic kinesin Eg5

p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis

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