Elevated cPLA<sub>2</sub> levels as a mechanism by which the p70 TNF and p75 NGF receptors enhance apoptosis

MacEwan, David J.

doi:10.1016/0014-5793(95)01495-0

Cited by 50 publications

(30 citation statements)

References 39 publications

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“…This response was reminiscent of the metabolic response seen with GM-CSF (28), a cytokine required for TF-1 cell proliferation, suggesting that TNF may induce cellular proliferation under these conditions. Maximal effects of TNF were seen at 30 ng/ml TNF (data not shown) consistent with other known responses (22,29).…”

Section: The Metabolic Effects Of Tnf On Tf-1 Cells Differ Depending supporting

confidence: 75%

“…Cells were then washed once by resuspension-centrifugation in culture medium (4°C), and DNA was stained by inclusion of 5 g/ml Hoechst 33342 stain as described (22). A 5-l aliquot of the stained cell sample was examined by epifluorescence using a Leitz Aristoplan microscope equipped with an A cube, and photographed at a magnification of ϫ 320.…”

Section: Analysis Of [ 3 H]thymidine Incorporation-[mentioning

confidence: 99%

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Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

Baxter

Kuo

Jupp

et al. 1999

Journal of Biological Chemistry

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The TF-1 human erythroleukemic cell line exhibits opposing physiological responses toward tumor necrosis factor-␣ (TNF) treatment, dependent upon the mitotic state of the cells. Mitotically active cells in log growth respond to TNF by rapidly undergoing apoptosis whereas TNF exposure stimulates cellular proliferation in mitotically quiescent cells. The concentrationdependent TNF-induced apoptosis was monitored by cellular metabolic activity and confirmed by both DNA epifluorescence and DNA fragmentation. Moreover, these responses could be detected by measuring extracellular acidification activity, enabling rapid prediction (within ϳ 1.5 h of TNF treatment) of the fate of the cell in response to TNF. Growth factor resupplementation of quiescent cells, resulting in reactivation of cell cycling, altered TNF action from a proliferative stimulus to an apoptotic signal. Expression levels of the type II TNF receptor subtype (p75TNFR) were found to correlate with sensitivity to TNF-induced apoptosis. Pretreatment of log growth TF-1 cells with a neutralizing antip75TNFR monoclonal antibody inhibited TNF-induced apoptosis by greater than 80%. Studies utilizing TNF receptor subtype-specific TNF mutants and neutralizing antisera implicated p75TNFR in TNF-dependent apoptotic signaling. These data show a bifunctional physiological role for TNF in TF-1 cells that is dependent on mitotic activity and controlled by the p75TNFR.Cells have the capability of responding to a multitude of signals that it encounters in its extracellular environment. One such signal with widespread pleiotropic actions is the cytokine tumor necrosis factor-␣ (TNF) 1 (1). TNF has been shown to modulate proliferation, differentiation, and apoptotic or necrotic cell death in a number of different cell types (2-4). These disparate responses to TNF are mediated by TNF binding to specific cell surface receptors. Two distinct TNF receptors, type I (p55TNFR) and type II (p75TNFR) (M r 55,000 -60,000 and 70,000 -80,000 in human cells, respectively), have been identified (5, 6), although it remains unclear which of the many responses reported for TNF can be attributed to a specific receptor subtype (4). Moreover, the precise signal transduction pathways for each of these receptor subtypes have yet to be fully delineated. One action of TNF, the induction of apoptosis, is characterized by a discrete set of cellular events regulated by gene expression (7,8). The physiological events accompanying apoptosis include condensation of the chromatin, degradation of DNA through the activation of endogenous nucleases, and dissolution of the cell into small membrane-bound apoptotic vesicles (9, 10). In vivo, these vesicles are phagocytosed by macrophages or other phagocytic cells. Cell death by apoptosis is essential in many physiological processes, including embryonic development of the nervous system (11), oncogenic pathology (12), and clonal selection of hematopoietic cells (13).Conversely, TNF has also been shown to stimulate cellular proliferation in a variety of systems...

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Section: The Metabolic Effects Of Tnf On Tf-1 Cells Differ Depending supporting

confidence: 75%

Section: Analysis Of [ 3 H]thymidine Incorporation-[mentioning

confidence: 99%

Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

Baxter

Kuo

Jupp

et al. 1999

Journal of Biological Chemistry

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“…NGFR, a TNF receptor having low affinity for NGF, was also induced by EGR2. Expression of NGFR can induce neural cell death (Minaguchi et al, 1999), and the presence of this receptor enhances TNF-induced apoptosis although TNFa is unable to bind to NGFR (MacEwan, 1996). Since NGFR was induced in all of our cell lines, whether EGR2-sensitive or -resistant, its role in the EGR2-induced death pathway, if any, remains unclear.…”

Section: Discussionmentioning

confidence: 88%

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Unoki

Nakamura

2003

Oncogene

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EGR2 plays a key role in the PTEN-induced apoptotic pathway. Using adenovirus-mediated gene transfer to 39 cancer cell lines, we found that EGR2 could induce apoptosis in a large proportion of these lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9. Analysis by cDNA microarray and subsequent functional studies revealed that EGR2 directly transactivates expression of BNIP3L and BAK. Our results helped to clarify the molecular mechanism of the apoptotic pathway induced by PTEN-EGR2, and suggested that EGR2 may be an excellent target molecule for gene therapy to treat a variety of cancers.

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“…An essential role for cPLA 2 has been proposed in cytotoxicity and apoptosis resulting from tumor necrosis factor (53,54) and ischemia in kidney (8) and brain (20). In the current study, we have demonstrated that expression of cPLA 2 , in cells with nonmeasurable baseline levels, results in enhanced susceptibility to H 2 O 2 -induced injury.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic Phospholipase A2 (PLA2), but Not Secretory PLA2, Potentiates Hydrogen Peroxide Cytotoxicity in Kidney Epithelial Cells

Sapirstein

Spech

Witzgall

et al. 1996

Journal of Biological Chemistry

132

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Phospholipase A 2 (PLA 2 ) and reactive oxygen species have been implicated both individually and synergistically in various forms of cellular injury. The form(s) of PLA 2 important for cell injury and the implications of enhanced activity of the enzyme, however, have not been discerned. Previous studies reveal an increase in PLA 2 activity associated with cell injury, but this association does not establish a causal relationship between the increase in activity and the injury. LLC-PK 1 cell lines were created that express either the cytosolic PLA 2 or a group II PLA 2 . The susceptibility of these cells to hydrogen peroxide toxicity was determined in order to evaluate the relative importance of these two forms of PLA 2 in oxidant injury. Expression of cytosolic PLA 2 in the LLC-cPLA 2 cell line was associated with a 50-fold increase in PLA 2 activity in the cytosolic fraction, an increase in agonist-stimulated arachidonate release, and immunodetection of the cytosolic PLA 2 protein that was undetectable in control cells. Exposure to hydrogen peroxide or menadione, but not mercuric chloride, resulted in significantly greater lactate dehydrogenase release in LLC-cPLA 2 cells when compared with control cells. Exogenous arachidonic acid (150 M) did not enhance hydrogen peroxide-induced injury. The intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/tetra(acetoxymethyl) ester, protected the cells against injury, but the calcium ionophore, A23187, did not increase injury. Glycine conferred no protective effect against hydrogen peroxide toxicity. By contrast to these results with cytosolic PLA 2 -expressing cells, secretory PLA 2 expression to very high levels did not increase susceptibility to hydrogen peroxide. Thus, cytosolic PLA 2 may an be an important mediator of oxidant damage to renal epithelial cells.

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Elevated cPLA₂ levels as a mechanism by which the p70 TNF and p75 NGF receptors enhance apoptosis

Cited by 50 publications

References 39 publications

Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Cytosolic Phospholipase A2 (PLA2), but Not Secretory PLA2, Potentiates Hydrogen Peroxide Cytotoxicity in Kidney Epithelial Cells

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Elevated cPLA2 levels as a mechanism by which the p70 TNF and p75 NGF receptors enhance apoptosis

Cited by 50 publications

References 39 publications

Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression

EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK

Cytosolic Phospholipase A2 (PLA2), but Not Secretory PLA2, Potentiates Hydrogen Peroxide Cytotoxicity in Kidney Epithelial Cells

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Elevated cPLA₂ levels as a mechanism by which the p70 TNF and p75 NGF receptors enhance apoptosis