Cadmium induced apoptosis in a human T cell line

Azzouzi, Bouchra El; Tsangaris, George Th.; Pellegrini, Olivier; Manuel, Y; Benveniste, Jacques; Thomas, Y

doi:10.1016/0300-483x(94)90115-5

Cited by 161 publications

(64 citation statements)

References 34 publications

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“…It is now clear that, in thymocytes and mature T cells, a calcium response occurs following a number of apoptotic stimuli, including ␥-irradiation (50), TCR and Fas ligation (51,52), toxic metals (53), as well as the removal of specific growth factors from culture medium (54). Calcium is believed to activate a number of calcium-binding proteins during apoptosis (55)(56)(57)(58) as well as calcium-dependent endonucleases that mediate DNA fragmentation (59 -61).…”

Section: Discussionmentioning

confidence: 99%

Calcium and Its Role in the Nuclear Translocation and Activation of Cytosolic Phospholipase A2 in Cells Rendered Sensitive to TNF-Induced Apoptosis by Cycloheximide

Draper

Harris

Culver

et al. 2004

The Journal of Immunology

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In these experiments, we investigated the role of calcium as a second messenger in the apoptotic activation of cytosolic phospholipase A2 (cPLA2). As our model, we used a murine fibroblast cell line (C3HA) that was induced to undergo apoptosis by a combination of TNF and cycloheximide. Using fura 2 Ca2+ imaging, we found strong evidence for an intracellular calcium response after 1 h of treatment, which correlated with the onset of phosphatidylserine externalization, but preceded effector procaspase processing by several hours. The response was strongest in the perinuclear region, where mean levels rose 83% (144 ± 14 nM in untreated cells vs 264 ± 39 nM in treated), while cells displaying morphological evidence of apoptosis had the highest levels of calcium (250–1000 nM). Verapamil blocked this response, indicating an extracellular source for the calcium. Fluorescence microscopy revealed a pattern of nuclear translocation of cPLA2 during apoptosis, which was also blocked by verapamil, indicating an important role for calcium in this process. In addition, we found that verapamil prevented the release of [3H]arachidonic acid from C3HA cells induced to undergo apoptosis by the chemotherapeutic agents vinblastine, melphalan, and cis-platinum. Together, these data suggest that calcium is important for cPLA2 activation by diverse apoptotic stimuli.

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Section: Discussionmentioning

confidence: 99%

Calcium and Its Role in the Nuclear Translocation and Activation of Cytosolic Phospholipase A2 in Cells Rendered Sensitive to TNF-Induced Apoptosis by Cycloheximide

Draper

Harris

Culver

et al. 2004

The Journal of Immunology

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“…Cadmium is a potent inducer of MT synthesis that not only acts through metal response elements of the MT gene to up-regulate gene transcription (Karin et al, 1984), but can also cause intracellular free radical generation and lipid peroxidation, DNA damage and a characteristic apoptotic response (El Azzouzi et al, 1994;Yang et al, 1997). Apoptosis induced by cadmium is preceded by the participation of oxidative stress, with up-regulation of oxidant stress genes such as glutathione S-transferase and g-glutamylcysteine synthetase, activation of redox sensitive transcription factor AP-1 and NF-kB, as well as induction of MT-1 and MT-II synthesis (Hart et al, 1999;Zhou et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the synthesis of MT was shown to be induced several-fold during oxidative stress (Sato and Bremner, 1993) to protect the cells against cytotoxicity (Aschner et al, 1998) and DNA damage (Cai et al, 1995). In particular, MT synthesis is induced following treatment with cadmium, an environmental pollutant that is able to cause oxidative stress, DNA damage and apoptosis (El Azzouzi et al, 1994;Yang et al, 1997). The protective role of MT may also depend on the nuclear/cytoplasmic localisation of MT in the cell.…”

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confidence: 99%

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Fan

Cherian

2002

Br J Cancer

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The expression and induction of metallothionein has been associated with protection against oxidative stress and apoptosis. This study examines the effect of tumour suppressor protein p53 on metallothionein expression following CdCl 2 treatment in eight human epithelial breast cancer cell lines differing in p53 and oestrogen-receptor status. Cells were treated with 10 mM CdCl 2 for 24 h and metallothionein protein levels were measured by cadmium binding assay. MCF7 cells which are p53-positive (p53+) and oestrogen-receptor-positive showed a large induction in metallothionein synthesis by 10.79+1.36-fold. Other breast cancer cell lines which are p53-negative (p537) and oestrogen-receptor-negative or weakly oestrogenreceptor-positive showed a small induction ranging from 1.40+0.10 to 3.65+0.30-fold. RT -PCR analysis showed an induction of metallothionein mRNA in MCF7 cells by about 1.61+0.08-fold, while in HCC1806 cells (p537, oestrogenreceptor-negative) by 1.11+0.13-fold, and in MDA-MB-231 (p537, oestrogen-receptor-negative) by 1.25+0.06-fold. Metallothionein localisation was determined by immunohistochemical staining. Prior to metal treatment, metallothionein was localised mainly in the cytoplasm of MCF7 and MDA-MB-231 cells. After treatment with 10 mM CdCl 2 for 24 h, MCF7 cells showed intense nuclear and cytoplasmic staining for metallothionein, while MDA-MB-231 cells showed staining in the cytoplasm with weak nuclear staining. Apoptosis induced by 10 -40 mM CdCl 2 at time points between 4 and 48 h was examined with TUNEL assay. In MCF7 cells, apoptosis increased with higher concentrations of CdCl 2 , it peaked at 6 -8 h and appeared again at 48 h for all concentrations of CdCl 2 tested. In MDA-MB-231 cells, apoptosis remained at low levels for 10 -40 mM CdCl 2 at all time points. Studies on cadmium uptake showed similar uptake and accumulation of cadmium at 8 and 24 h in all the cell lines. The data demonstrate that treatment of epithelial breast cancer cells with 10 mM CdCl 2 for 24 h caused a greater induction of metallothionein protein and mRNA expression in p53+ and oestrogen-receptor-positive cells as compared to p537 and oestrogen-receptor-negative or weakly oestrogen-receptor-positive cells. This effect may be associated with the occurrence of apoptosis and suggests a role for p53 and oestrogen-receptor on the expression and induction of metallothionein in epithelial cells.

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“…Cadmium can induce cell death either by necrotic or by apoptotic mechanisms. This metal was shown to induce apoptosis only in distinct cell types (2,3). In some instances, cadmium even protected from apoptosis caused by other agents (4).…”

mentioning

confidence: 99%