Role of Calcium Ion in Induction of Apoptosis by Etoposide in Human Leukemia HL-60 Cells

Yoshida, Akira; Ueda, Takanori; Takauji, Rumiko; Liu, Yunpeng; Fukushima, Takao; Inuzuka, Manabu; Nakamura, Tõru

doi:10.1006/bbrc.1993.2338

Cited by 35 publications

(24 citation statements)

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“…3A, compare lanes 1, 5, 7, and 9). Treatment of cells with the anticancer drug etoposide, a DNA-damaging agent, results in the induction of apoptosis (5,63). In 220-8 PKC transfectants, etoposide-induced apoptosis was associated with cleavage of PKC to a 50-kDa fragment (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Cη

Morrow

Muljo

Zhang

et al. 1999

Molecular and Cellular Biology

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Using a subtractive cloning scheme on cDNA prepared from primary pro-B and pre-B cells, we identified several genes whose products regulate apoptosis. We further characterized one of these genes, encoding protein kinase C (PKC). PKC transcripts were readily detected in pro-B cells but were absent in pre-B cells. Although both a full-length and a truncated form of PKC were detectable in bone marrow pro-B cells, transition to the pre-B-cell stage was associated with increased relative levels of truncated PKC. We found that PKC is proteolyzed in apoptotic lymphocytes, generating a kinase-active fragment identical to the truncated form which is capable of inducing apoptosis when expressed in a pro-B cell line. Caspase-3 can generate an identical PKC cleavage product in vitro, and caspase inhibitors prevent the generation of this product during apoptosis in transfected cell lines. Inducible overexpression of either the full-length or truncated form of PKC results in cell cycle arrest at the G 1 /S transition. These results suggest that the expression and proteolytic activation of PKC play an important role in the regulation of cell division and cell death during early B-cell development.

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Section: Resultsmentioning

confidence: 99%

Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Cη

Morrow

Muljo

Zhang

et al. 1999

Molecular and Cellular Biology

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“…1 TPCK also blocks`apoptotic nuclei promoting activity' induced by Fas antigen ligation in T-cells 2 thus preventing anti-Fas-induced apoptosis. 3 Etoposide-induced DNA fragmentation in HL60 cells is also inhibited 4 and TPCK-sensitive proteases have been described, that appear to be specifically involved in DNA fragmentation induced by treatment of human myelogenous leukemia ML-1a cells with TNF. 5 Also LPSinduced cytotoxicity in macrophages could be prevented by TPCK.…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

et al. 1999

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The serine protease inhibitor N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) can interfere with cell-cycle progression and has also been shown either to protect cells from apoptosis or to induce apoptosis. We tested the effect of TPCK on two transformed T-cell lines. Both Jurkat T-cells and Theileria parva-transformed T-cells were shown to be highly sensitive to TPCK-induced growth arrest and apoptosis. Surprisingly, we found that the thiol antioxidant, Nacetylcysteine (NAC), as well as L-or D-cysteine blocked TPCK-induced growth arrest and apoptosis. TPCK inhibited constitutive NF-kB activation in T. parva-transformed T-cells, with phosphorylation of IkBa and IkBb being inhibited with different kinetics. TPCK-mediated inhibition of IkB phosphorylation, NF-kB DNA binding and transcriptional activity were also prevented by NAC or cysteine. Our observations indicate that apoptosis and NF-kB inhibition induced by TPCK result from modifications of sulphydryl groups on proteins involved in regulating cell survival and the NF-kB activation pathway(s).

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“…This was an unexpected result because etoposide-induced DNA fragmentation was blocked by TPCK in an earlier study. 29,50 An additional pathway involving serine protease(s) may be present upstream of CAD/DFF40 activation.…”

Section: Discussionmentioning

confidence: 99%

Properties of DNA fragmentation activity generated by ATP depletion

Nakamura

Wada

2000

Cell Death Differ

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Internucleosomal DNA fragmentation is generally perceived as one of the characteristic features of apoptosis, most of which are driven by caspase activation dependent upon ATP. On the other hand, ATP depletion has been reported to induce apoptosis accompanying DNA fragmentation. To address this apparent paradox, we analyzed the DNA-fragmenting activity generated in ATP-depleted cells. In HL-60 promyelocytic leukemia cells cultured in glucose-free medium with oligomycin, internucleosomal DNA fragmentation occurred as an early event. The DNA fragmentation was blocked by serine protease inhibitors but not by caspase inhibitors. Consistently, ICAD/DFF45 could not inhibit the DNAfragmenting activity of the ATP-depleted cytosol in a cell-free system. When ATP was supplied to the cell-free assay, 80% of the DNA-fragmenting activity was lost. The reduced activity was then restored by proteasome inhibitors, suggesting a role of proteasome to protect from a cellular insult derived from ATP-depletion. Cell Death and Differentiation (2000) 7, 477 ± 484.

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Role of Calcium Ion in Induction of Apoptosis by Etoposide in Human Leukemia HL-60 Cells

Cited by 35 publications

References 0 publications

Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Cη

Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Cη

N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

Properties of DNA fragmentation activity generated by ATP depletion

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