Prevention of necrosis and activation of apoptosis in oxidatively injured human myeloid leukemia U937 cells

Palomba, Letizia; Sestili, Piero; Cattabeni, F.; Azzi, Angelo; Cantoni, Orazio

doi:10.1016/0014-5793(96)00634-5

Cited by 48 publications

(34 citation statements)

References 15 publications

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“…This finding is consistent with earlier reports showing that H 2 O 2 can kill cells by mechanisms that do not depend upon ATP depletion or activation of PARP (39,40). Additional pathways responsible for H 2 O 2 -induced cell death have been defined (41) and probably depend on iron-mediated formation of secondary radicals (42,43).…”

Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 92%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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Apoptosis and necrosis are two forms of cell death that are induced under different conditions and that differ in morphological and biochemical features. In this report, we show that, in the presence of oxidative stress, human B lymphoma cells are unable to undergo apoptosis and die instead by a form of necrosis. This was established using the chemotherapy drug VP-16 or the calcium ionophore A23187 to induce apoptosis in Burkitt's lymphoma cell lines and by measuring classical markers of apoptotic death, including cell morphology, annexin V binding, DNA ladder formation, and caspase activation. In the presence of relatively low levels of H 2 O 2 (75-100 M), VP-16 and A23187 were unable to induce apoptosis in these cells. Instead, the cells underwent non-apoptotic cell death with mild cytoplasmic swelling and nuclear shrinkage, similar to the death observed when they were treated with H 2 O 2 alone. We found that H 2 O 2 inhibits apoptosis by depleting the cells of ATP. The effects of H 2 O 2 can be overcome by inhibitors of poly(ADP)-ribosylation, which also preserve cellular ATP levels, and can be mimicked by agents such as oligomycin, which inhibit ATP synthesis. The results show that oxidants can manipulate cell death pathways, diverting the cell away from apoptosis. The potential physiological ramifications of this finding will be discussed.

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Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 92%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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“…4). Our results are supported by a recent report demonstrating that H 2 O 2 -induced necrotic cell death in U937 cells can also be modulated by the addition of the PARP inhibitor 3AB (49). Here, we also show that one of the recruited signaling pathways is dependent on de novo protein synthesis.…”

Section: H 2 O 2 Induces a Programmed Neuronal Death Distinct Fromsupporting

confidence: 91%

Oxidative Stress Induces Neuronal Death by Recruiting a Protease and Phosphatase-gated Mechanism

Sée¹,

Loeffler²

2001

Journal of Biological Chemistry

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Reactive oxygen species (ROS) cause death of cerebellar granule neurons. Here, a 15-min pulse of H 2 O 2 (100 M) induced an active process of neuronal death distinct from apoptosis. Oxidative stress activated a caspaseindependent but calpain-dependent decline of calcium/ calmodulin-dependent protein kinase IV and cAMPresponsive element-binding protein (CREB). Calpain inhibitors restored calcium/calmodulin-dependent protein kinase IV and CREB but did not influence phosphorylated CREB levels or survival, indicating recruitment of an additional dephosphorylation process. Co-treatment with calpain and serine/threonine phosphatase inhibitors restored pCREB levels and rescued neurons. This phosphatase-activated signaling pathway was shown to be dependent on de novo protein synthesis. Further, gene transfer studies revealed that CREB is a common final effector of both apoptosis and ROS-induced death. Our data indicate that dephosphorylation and proteolytic signaling mechanisms underlie ROS-induced programmed cell death.

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“…There is also direct evidence that generation of O 2 -. and hydrogen peroxide in cell-free systems causes tumour cell killing (Ioannidis and de Groot, 1993;Palomba et al, 1996). In humans, there is indirect evidence that spontaneous cytotoxicity of monocytes towards tumour cells may be associated with their ability to produce ROI (Davies and Edwards, 1992;Martin and Edwards, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The direct evidence for the importance of ROI in the killing of tumour cells comes from the cell-free systems generating hydrogen peroxide or superoxide anion (O 2 -. ) (Ioannidis and de Groot, 1993;Palomba et al, 1996). TIM from mouse mammary carcinomas are able to produce ROI (Mantovani et al, 1992).…”

mentioning

confidence: 99%

Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

et al. 1999

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SummaryThe present study examined the ability of human monocytes to produce reactive oxygen intermediates after a contact with tumour cells. Monocytes generated oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide anion production, after stimulation with the tumour, but not with untransformed, cells. The use of specific oxygen radical scavengers and inhibitors, superoxide dismutase, catalase, dimethyl sulphoxide and deferoxamine as well as the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide, indicated that chemiluminescence was dependent on the production of superoxide anion and hydroxyl radical and the presence of myeloperoxidase. The tumour cell-induced chemiluminescent response of monocytes showed different kinetics from that seen after activation of monocytes with phorbol ester. These results indicate that human monocytes can be directly stimulated by tumour cells for reactive oxygen intermediate production. Spontaneous monocyte-mediated cytotoxicity towards cancer cells was inhibited by superoxide dismutase, catalase, deferoxamine and hydrazide, implicating the role of superoxide anion, hydrogen peroxide, hydroxyl radical and hypohalite. We wish to suggest that so-called 'spontaneous' tumoricidal capacity of freshly isolated human monocytes may in fact be an inducible event associated with generation of reactive oxygen intermediates and perhaps other toxic mediators, resulting from a contact of monocytes with tumour cells.

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Prevention of necrosis and activation of apoptosis in oxidatively injured human myeloid leukemia U937 cells

Cited by 48 publications

References 15 publications

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Oxidative Stress Induces Neuronal Death by Recruiting a Protease and Phosphatase-gated Mechanism

Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

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