Protease inhibitors block apoptosis at intermediate stages: a compared analysis of DNA fragmentation and apoptotic nuclear morphology

Ghibelli, Lina; Maresca, Vittoria; Coppola, Simona; Gualandi, G

doi:10.1016/0014-5793(95)01284-2

Cited by 49 publications

(27 citation statements)

References 28 publications

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“…Unexpectedly, in some preliminary experiments using a U937 cell line of different origin in respect to that utilized in all the experiments shown in this report, while all other assays showed the presence of apoptotic cells in cultures infected with HSV-2, only the gel electrophoresis technique did not give the same result (data not shown). We were unable to understand the exact reasons for this discrepancy, but they are probably related to a characteristic peculiar to the cell line utilized, as previously described for U937 following a different inducing stimulus (Ghibelli et al, 1995). However, no evidence of cell death other than optosis was observed in cultures of U937 cells infected with herpes simplex viruses and analyzed in the above-reported or in any other experiment.…”

Section: Herpes Simplex Type 2 Does Not Induce Apoptosis In Vero Cellsmentioning

confidence: 73%

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

et al. 1997

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Increasing evidence indicates that apoptosis can be associated with several viral infections. Here we demonstrate, that infection of monocytoid cells by Herpes simplex virus 2 (HSV-2) resulted, in time-and dose-dependent induction of apoptosis as an exclusive cytopathic effect. The phenomenon was confirmed using four different techniques. Conversely, apoptosis was not observed in the Vero cell line. Virus yield in monocytoid cells was delayed and reduced, although well detectable, in comparison with that observed in Vero cells. Nevertheless, released virions exhibited full infecting capability. Apoptosis induced by HSV-2 was not inhibited by cycloheximide and only partially by an UV-treatment which completely abrogated infectivity. Virus-induced apoptosis was partly inhibited by indomethacin and was associated with a down-regulation of Bcl-2. A similar, but less pronounced, apoptosis-inducing effect in monocytoid cells was also observed with HSV-1 infection. Depending on the target cells, therefore, HSV could complete a cycle of infection which is characterized by apoptosis of infected cells.

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Section: Herpes Simplex Type 2 Does Not Induce Apoptosis In Vero Cellsmentioning

confidence: 73%

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

et al. 1997

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“…Some protease inhibitors have been shown to inhibit apoptosis in the early stages of apoptosis [39]. Among these inhibitors, serine protease inhibitor has been used to block TBT-induced apoptosis at an intermediate stage for experiments involving morphological observation [39]. According to our microarray results, the five inhibitor genes of T. thermophila were all up-regulated after exposure to TBT.…”

Section: Identification Of Differentially Expressed Genes and Categormentioning

confidence: 81%

“…TBT has been reported to cause apoptosis [36,37], in which activation of protease is known to play an important role [38]. Some protease inhibitors have been shown to inhibit apoptosis in the early stages of apoptosis [39]. Among these inhibitors, serine protease inhibitor has been used to block TBT-induced apoptosis at an intermediate stage for experiments involving morphological observation [39].…”

Section: Identification Of Differentially Expressed Genes and Categormentioning

confidence: 99%

Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Chang

Feng

Miao

2011

Sci. China Life Sci.

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Dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are persistent in the environment and cause continuous toxic effects in humans and aquatic life. Tetrahymena thermophila has the potential for use as a model for research regarding toxicants. In this study, this organism was used to analyze a genome-wide microarray generated from cells exposed to DDT, TBT and TCDD. To accomplish this, genes differentially expressed when treated with each toxicant were identified, after which their functions were categorized using GO enrichment analysis. The results suggested that the responses of T. thermophila were similar to those of multicellular organisms. Additionally, the context likelihood of relatedness method (CLR) was applied to construct a TCDD-relevant network. The T-shaped network obtained could be functionally divided into two subnetworks. The general functions of both subnetworks were related to the epigenetic mechanism of TCDD. Based on analysis of the networks, a model of the TCDD effect on T. thermophila was inferred. Thus, Tetrahymena has the potential to be a good unicellular eukaryotic model for toxic mechanism research at the genome level. microarray, enrichment analysis, gene interaction network, pollutant Citation:Chang Y, Feng L F, Miao W. Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Sci China Life Sci, 2011, 54: 617 -625,

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“…Whilst ICE-like proteases are responsible for cleavage of some of these substrates, such as PARP, other proteases are also involved. Introduction of exogenous proteases into cells induces morphological and biochemical changes characteristic of apoptosis (Williams and Henkart, 1994) and various protease inhibitors block apoptosis in different cell types (Bruno et al, 1992;Chow et al, 1995;Ghibelli et al, 1995;Kaufmann et al, 1993;Sarin et al, 1993;Squier et al, 1994;Suffys et al, 1988;Zhivotovsky et al, 1995). Much interest has focused on ICE due to its structural similarity to ced-3 (Yuan et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in human monocytic THP.1 cells involves several distinct targets of N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK)

et al. 1997

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N-Tosyl-L-phenylalanyl chloromethyl ketone (TPCK), a chymotrypsin-like serine protease inhibitor, affected apoptosis in human monocytic THP.1 cells differently dependent on both the concentration used and the apoptotic stimulus. TPCK (50 ± 75 mM) induced both biochemical and ultrastructural changes characteristic of apoptosis, including proteolysis of poly (ADP-ribose) polymerase (PARP) and lamins together with formation of large kilobase pair fragments of DNA, particularly of 30 ± 50 and 200 ± 300 kilobase pairs in length but without internucleosomal cleavage of DNA. The induction of apoptosis by TPCK also involved the processing of CPP32 and Mch 3 to their catalytically active subunits. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.FMK), an ICE-like protease inhibitor, completely prevented all the biochemical and morphological changes induced by TPCK demonstrating the involvement of ICE-like proteases in the execution phase of apoptosis. Lower concentrations of TPCK (5 ± 20 mM) prevented internucleosomal cleavage of DNA induced by other apoptotic stimuli. TPCK (10 mM) inhibited cell death induced by etoposide but potentiated that induced by cycloheximide demonstrating that it differentially affected apoptosis in THP.1 cells dependent on the stimulus used. These results are consistent with at least three distinct TPCK targets, one being important for cell survival, the second in facilitating internucleosomal cleavage of DNA and the third in the modulation of apoptosis induced by different apoptotic stimuli.

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Protease inhibitors block apoptosis at intermediate stages: a compared analysis of DNA fragmentation and apoptotic nuclear morphology

Cited by 49 publications

References 28 publications

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

Herpes simplex virus 2 causes apoptotic infection in monocytoid cells

Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Apoptosis in human monocytic THP.1 cells involves several distinct targets of N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK)

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