Zinc Ions Prevent Processing of Caspase-3 during Apoptosis Induced by Geranylgeraniol in HL-60 Cells

Aiuchi, Toshihiro; Mihara, Saori; Nakaya, Mie; Masuda, Yutaka; Nakajo, Shigeo; Nakaya, Kazuyasu

doi:10.1093/oxfordjournals.jbchem.a022111

Cited by 62 publications

(31 citation statements)

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“…These observations fit well with the Zn 2+ -mediated inhibition of various caspases, including caspase-3 and caspase-6, previously reported by other groups. 21,22,31 In our experimental conditions, Zn 2+ -mediated inhibition of Mn 2+ -induced caspase-3 activation was associated with decrease in the amounts of both p19 and p17, the active fragments of caspase-3. As cleavage of the p19 form to the 17 kDa fragment is dependent on the autocatalytic activity of caspase-3, 23,37 it is possible that Zn 2+ -mediated inhibition of PARP cleavage is associated with a decrease in the production of the active p19 fragment.…”

Section: Cell Death and Differentiationmentioning

confidence: 64%

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Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)

et al. 2001

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Divalent cations, including Zinc and Manganese ions, are important modulators of cell activation. We investigated the ability of these two divalent cations to modulate apoptosis in human Burkitt lymphoma B cells line (Ramos). We found that Zinc (from 10 to 50 mM) inhibited Manganese-induced caspase-3 activation and apoptosis of Ramos cells. Higher concentration of Zinc (50 to 100 mM) did not prevent Manganese-mediated apoptosis but rather increased cell death among Ramos cells. This Zinc-mediated cell death was associated with apoptotic features such as cell shrinkage, the presence of phosphatidylserine residues on the outer leaflet of the cells, chromatin condensation, DNA fragmentation and decrease of mitochondrial transmembrane potential. Zincmediated apoptosis was associated with caspase-9 and caspase-3 activation as revealed by the appearance of active p35 fragment of caspase-9 and p19 and p17 of caspase-3 as well as in vivo cleavage of PARP and of a cell-permeable fluorogenic caspase-3 substrate (Phiphilux-G 1 D 2 ). Both Zincmediated apoptosis and caspase-3 activation were prevented by the cell-permeable, broad-spectrum inhibitor of caspases (zVAD-fmk) or overexpression of bcl-2. In addition, we show that Zinc-induced loss of transmembrane mitochondrial potential is a caspase-independent event, since it is not modified by the presence of zVAD-fmk, which is inhibited by overexpression of bcl-2. These results indicate that depending on its concentration, Zinc can exert opposite effects on caspase-3 activation and apoptosis in human B lymphoma cells: concentrations below 50 mM inhibit caspase-3 activation and apoptosis whereas higher concentrations of Zinc activate a death pathway associated with apoptotic-like features and caspase-3 activation. Cell Death and Differentiation (2001) 8, 152 ± 161.

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Section: Cell Death and Differentiationmentioning

confidence: 64%

“…30 Several groups have reported that Zn 2+ inhibits caspase-3 activity and apoptosis. 20,21,31 We first studied the effect of various doses of Zn 2+ on Mn 2+ -induced death of Ramos cells. Apoptosis was followed by measuring cell shrinkage or chromatin condensation evidenced by the appearance of hypodiploid nuclei.…”

Section: Resultsmentioning

confidence: 99%

Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)

et al. 2001

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“…Although we did not examine the relationship between intracellular labile Zn and caspase-3 activation, a Zn chelator attenuated Py/Zn-induced apoptosis and PARP proteolysis, a sign that caspases, including caspase-3, have been activated. 16) Moreover, an inhibitor of caspase-3 decreased the appearance of DNA fragmentation (Fig. 3), suggesting that the activation of caspase-3 is at least partly responsible for the induction of apoptosis by Py/Zn in HL-60 cells.…”

Section: Discussionmentioning

confidence: 87%

“…16) To confirm the activation of caspase-3 during apoptosis induced by Py (1 mM) plus Zn (25 mM) in HL-60 cells, we examined caspase-3 activity in Py/Zntreated cells. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibitory effects of Zn on the induction of apoptosis were observed with inhibition of apoptotic stimuli-mediated activation of caspase-3. [14][15][16] Previously, we found that an influx of Zn into the cell, which was mediated by a Zn ionophore (Py, pyrithione) and Zn, induced apoptosis via activation of caspases in human leukemia HL-60 cells. 17) Although a broad-spectrum inhibitor of caspases attenuated Py/Zn-induced apoptosis, the involvement of caspase-3 in Py/Zn-induced apoptosis is obscure.…”

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confidence: 99%

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Activation of Caspase-3 in HL-60 Cells Treated with Pyrithione and Zinc

Kondoh

Tasaki

Takiguchi

et al. 2005

Biological & Pharmaceutical Bulletin

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The transition metal zinc (Zn) is an endogenous regulator of apoptosis. The ability of Zn to modulate apoptosis is believed to be mediated by the regulation of caspase activity. Previously, we reported that an acute influx of labile Zn induced apoptosis via activation of caspase in human leukemia HL-60 cells treated with a Zn ionophore (Py, pyrithione) and Zn at 1 and 25 m mM, respectively. In the present study, we investigated the involvement of caspase-3 in Py (1 m mM)/Zn (25 m mM)-induced apoptosis in HL-60 cells. Pro-caspase-3 is an inactive form of caspase-3. The processing of pro-caspase-3, a sign of caspase-3 activation, occurred 6 h after treatment with Py/Zn. Proteolysis of poly (ADP-ribose) polymerase (PARP), a substrate of caspase-3, was also observed 6 h after treatment with Py/Zn. We also confirmed the elevation of caspase-3 activity as an index of the cleavage of amino acid sequences recognized by activated caspase-3. An inhibitor of caspase-3 attenuated the appearance of the DNA ladder. Taken together, these results indicate that the activation of caspase-3 is partly responsible for the induction of apoptosis in Py/Zn-treated HL-60 cells.

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Protein synthesis-dependent but Bcl-2-independent cytochrome C release in zinc depletion-induced neuronal apoptosis

2000

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Previously, we reported that chelation of intracellular zinc with N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine (TPEN)‐induced macromolecule synthesis‐dependent apoptosis of cultured cortical neurons. According to the current theory of apoptosis, release of mitochondrial cytochrome C into the cytosol is required for caspase activation. In the present study, we examined whether cytochrome C release is dependent on macromolecule synthesis. Exposure of cortical cultures to 2 μM TPEN for 24 hr induced apoptosis as previously described. Fluorescence immunocytochemical staining as well as immunoblots of cell extracts revealed the release of cytochrome C into the cytosol 18–20 hr after the exposure onset. The cytochrome C release was completely blocked by the addition of cycloheximide or actinomycin D. Addition of the caspase inhibitor zVAD‐fmk did not attenuate the cytochrome C release, whereas it blocked TPEN‐induced apoptosis. Because Bcl‐2 has been shown to block cytochrome C release potently, we exposed human neuroblastoma cells (SH‐SY5Y) to TPEN. Whereas Bcl‐2 overexpression completely blocked both cytochrome C release and apoptosis induced by staurosporine, it attenuated neither induced by TPEN. The present results suggest that, in neurons, macromolecule synthesis inhibitors act upstream of cytochrome C release to block apoptosis and that, in addition to the classical Bcl‐2 sensitive pathway, there may exist a Bcl‐2‐insensitive pathway for cytochrome C release. J. Neurosci. Res. 61:508–514, 2000. © 2000 Wiley‐Liss, Inc.

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Zinc Ions Prevent Processing of Caspase-3 during Apoptosis Induced by Geranylgeraniol in HL-60 Cells

Cited by 62 publications

References 0 publications

Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)

Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)

Activation of Caspase-3 in HL-60 Cells Treated with Pyrithione and Zinc

Protein synthesis-dependent but Bcl-2-independent cytochrome C release in zinc depletion-induced neuronal apoptosis

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