Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line

Verhaegen, Steven; McGowan, Adrian J.; Brophy, Alan R.; Fernandes, Richard S.; Cotter, Thomas G.

doi:10.1016/0006-2952(95)00233-p

Cited by 168 publications

(105 citation statements)

References 42 publications

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“…Furthermore, a number of antioxidant compounds prevented DNA fragmentation and apoptosis in these cell lines [23,24]. As mentioned above, PARP cleavage has been linked to endonuclease activity and DNA fragmentation.…”

Section: Introductionmentioning

confidence: 85%

“…As a positive control for PARP cleavage, Jurkat T-cells were treated with 1 ~tg/ml antiFas antibody for 2 h (anti-Fas CH-11 IgM, Medical and Biological Laboratories, USA). Anti-oxidants were prepared as previously described [22][23][24] and the ones chosen were zinc chloride, 1 M in 0.15 saline, pyrrolidine dithiocarbamate (PDTC), 1 M in distilled water, butylated hydroxyanisole (BHA) and phenanthroline (Phen. ), 1 M in ethanol, 2,2,6,6-tetramethylpiperidinoxyl (Tempo.)…”

Section: Uv-and Drug-induced Apoptosismentioning

confidence: 99%

“…Cells were subsequently incubated for 30 min at room temperature in the dark. Stained cells were rinsed in PBS before analysis for fluorescence using a Becton Dickinson FACScan [24]. Bio-16-dUTP and the TdT-enzyme were obtained from Boehringer Mannheim.…”

Section: Dna Nick-end Labelling ( Tunel)mentioning

confidence: 99%

“…We utilised the following anti-oxidants, previously shown to inhibit apoptosis in our cell lines [22][23][24], zinc chloride, PDTC, Dox., Tempo., BHA, and Phen. Peroxide production was detected as early as 10-15 min in HL-60 cells and this was evident with all of the cytotoxic agents used in this study (Fig.…”

Section: Roi Parp Cleavage and Apoptosismentioning

confidence: 99%

“…To establish further that PARP cleavage and DNA fragmentation follow the same common pathway to apoptosis, protease inhibitors were tested against both PARP cleavage and DNA fragmentation. Given the protection observed with anti-oxidants against DNA fragmentation and apoptosis in these cells [22][23][24], we screened a range of anti-oxidants for the ability to prevent PARP cleavage. Our results indicate that both of these events (PARP cleavage and DNA fragmentation) occur following ROI production and suggest that ROI may act as common mediators, for PARP cleavage, DNA fragmentation and the eventual apoptosis of these leukaemic cells.…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen intermediate(s) (ROI): Common mediator(s) of poly(ADP‐ribose)polymerase (PARP) cleavage and apoptosis

McGowan¹,

Ruiz‐Ruiz²,

Gorman³

et al. 1996

FEBS Letters

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HL-60 acute myeioblastic and U937 monoblastoid lenkaemic cell lines both cleave poly(ADP-ribose)polymerase (PARP), at the onset of apoptosis, in response to a wide range of cytotoxic agents. This appears to be a common feature of leukaemic cell apoptusis. However, in the chronic myelogenous leukaemic (CML) derived cell line, K562, no such cleavage was detectable. This correlated with previous findings that this cell line is particularly resistant to apoptosis induced by cytotoxic agents. Proteolytic cLeavage of PARP and the subsequent progression to apoptosis was inhibited by two protease inhihiturs NEM and IOD. As both PARP cleavage and DNA fragmentation appeared cLosely linked in these cell lines, anti-oxidants (previously shown to be effective inhibitors of DNA fragmentation and apoptosis) were also demonstrated to prevent PARP cleavage. These results combine to suggest that ROI may mediate PARP cleavage, DNA fragmentation and the eventual apoptosis of these cells following cytotoxic insult.

show abstract

Section: Introductionmentioning

confidence: 85%

Section: Uv-and Drug-induced Apoptosismentioning

confidence: 99%

Section: Dna Nick-end Labelling ( Tunel)mentioning

confidence: 99%

Section: Roi Parp Cleavage and Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen intermediate(s) (ROI): Common mediator(s) of poly(ADP‐ribose)polymerase (PARP) cleavage and apoptosis

McGowan¹,

Ruiz‐Ruiz²,

Gorman³

et al. 1996

FEBS Letters

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Use of flow cytometry techniques in studying mechanisms of apoptosis in leukemic cells

et al. 1997

Self Cite

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The use of flow cytometric techniques has significantly aided the rapid advancement of our understanding of the process of apoptosis. Our laboratory is currently involved in investigating the ways in which cells can be induced to die and some of the signals that may be involved. To this end, we are using flow cytometry to detect apoptosis in cell cultures and to measure intracellular changes that occur during apoptosis, in particular, alterations in parameters such as mitochondrial function, oxidative stress, and gene expression. In this review of recent and ongoing research in our laboratory, we outline our studies on mechanisms of apoptosis by cytotoxic drugs, particularly in relation to the involvement of oxidative stress. In addition, we are studying the increased sensitivity to apoptosis seen in K652 cells that have been transfected with the p53 gene. Cytometry 29:97–105, 1997. © 1997 Wiley‐Liss, Inc.

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Activation of p38 mitogen-activated protein kinase and mitochondrial Ca2+-mediated oxidative stress are essential for the enhanced expression ofgrp78 induced by the protein phosphatase inhibitors okadaic acid and calyculin A

et al. 2000

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We have reported that treatment with okadaic acid, a potent protein phosphatase inhibitor, has the ability to enhance the synthesis of the 78-kDa glucose-regulated protein (GRP78). This article reports our investigation of another protein phosphatase inhibitor, calyculin A, demonstrating the signaling pathways elicited by the protein phosphatase inhibitors that lead to the induction of grp78. Our data showed that the induction process is abolished by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38(MAPK)). Phosphorylation-activation of p38(MAPK) in the treated cells was indicated by its own phosphorylation, as shown by double Western blotting analyses and directly confirmed by the in vitro kinase assay using MAPK-activated protein kinase-2, a well-known downstream effector of p38(MAPK), as a substrate. The involvement of p38(MAPK) in this process is further substantiated by using transient transfection assays with a plasmid, pGRP78-Luc, which contains a 0.72-kbp stretch of the grp78 promoter. By exploiting the same transfection assay, we demonstrated that the up-regulation of the grp78 promoter by the protein phosphatase inhibitors is suppressed in the presence of the cytoplasmic calcium chelator bis(aminophenoxy)ethane N,N'-tetraacetic acid, the mitochondria calcium uniporter inhibitor ruthenium red as well as the antioxidants N-acetyl cysteine and pyrrolidinedithiocarbamate. Taken together, our results lead us to conclude that treatment with the protein phosphatase inhibitors would activate the signaling pathways involving p38(MAPK) and mitochondrial calcium-mediated oxidative stress and that these pathways must act in concert in order to confer the induction of grp78 by okadaic acid and calyculin A.

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Inhibition of apoptosis by antioxidants in the human HL-60 leukemia cell line

Cited by 168 publications

References 42 publications

Reactive oxygen intermediate(s) (ROI): Common mediator(s) of poly(ADP‐ribose)polymerase (PARP) cleavage and apoptosis

Reactive oxygen intermediate(s) (ROI): Common mediator(s) of poly(ADP‐ribose)polymerase (PARP) cleavage and apoptosis

Use of flow cytometry techniques in studying mechanisms of apoptosis in leukemic cells

Activation of p38 mitogen-activated protein kinase and mitochondrial Ca2+-mediated oxidative stress are essential for the enhanced expression ofgrp78 induced by the protein phosphatase inhibitors okadaic acid and calyculin A

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