Ionophore-induced apoptosis: Role of DNA fragmentation and calcium fluxes

Ojcius, David M.; Zychlinsky, Arturo; Zheng, Lan; Young, John Ding‐E

doi:10.1016/0014-4827(91)90477-c

Cited by 233 publications

(125 citation statements)

References 42 publications

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“…Changes in the membrane potential are presumed to be due to the opening of the mitochondrial permeability transition pores that play a central role in apoptosis (Green and Reed, 1998). Intracellular calcium fluxes are also thought to be involved in the induction of apoptosis (Ojcius et al, 1991). An increase in reactive oxygen species has also been linked to the initiation of the apoptotic cascade (Garland and Halestrap, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The effect was monitored using mobilization of intracellular calcium, loss of mitochondrial membrane potential and increase in reactive oxygen species as markers of apoptosis over a 24 hour period after exposure. All these events have been clearly linked with induction of apoptosis (Ojcius et al, 1991;Garland and Halestrap, 1997;Kroemer et al, 1997;Green and Reed, 1998). In addition, we have previously shown that treatment with anti-oxidants, L-Lactate and L-Deprenyl, prevented the bystander effect in ICCM exposed HPV-G cells .…”

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confidence: 99%

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Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Lyng¹,

Seymour²,

Mothersill³

2000

Br J Cancer

243

154

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Summary This study investigated the ability of medium from irradiated cells to induce early events in the apoptotic cascade, such as mobilization of intracellular calcium, loss of mitochondrial membrane potential and increase in reactive oxygen species, in cells which were never exposed to radiation. Medium from irradiated human keratinocytes was harvested and transferred to unirradiated keratinocytes. Endpoints characteristic of the initiation of apoptosis were monitored for a period of 24 h following medium transfer. Clonogenic survival was also measured. Rapid calcium fluxes (within 30 s), loss of mitochondrial membrane potential, increases in reactive oxygen species (from 6 h after medium transfer), an increase in the number of apoptotic cells (48 hours after medium transfer) and a marked reduction in clonogenic survival (after 9 days) were observed. There was no significant difference between medium generated by cells irradiated at 0.5 Gy or 5 Gy. The data suggest that initiating events in the apoptotic cascade were induced in unexposed cells by a signal produced by irradiated cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Lyng¹,

Seymour²,

Mothersill³

2000

Br J Cancer

243

154

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“…(i) High dose IL-2 stimulation results in a conspicuous hypertrophy of the cells due to a tremendous build-up of intracellular glycogen volume in addition to a general expansion of cytoplasmic constituents including the specific granules; (ii) concomitantly with the gradual morphological transformation the cells unexpectedly lost their in vitro cytolytic efficiency which stands in contrast with the previosly reported enhanced cytotoxicity of A-NK cells [10], and is seemingly in conflict with the intracellular expansion of the assumed cytolytic effector structures, the two-compartment granules [12][13][14][15][16][17]; (iii) direct observations clearly indicated that these changes were associated with an altered interaction pattern with tumour target cells in vitro, the large A-NK cells from the latter half of the culture period causing an active retraction or a release of anchored B16 cells from the culture surface instead of binding to the target cells; (iv) it has not been demonstrated previously that PGs are spaced into a three-dimensional macromolecular network within the dense cores of two-compartment granules and (v) the timed EM observations provide information on the morphogenesis, maturation and further differentiation of specific granules. These results thus emphasize that propagation of murine spleen lymphocytes during intermittent supplementation with a high dose IL-2 does not establish a functionally and morphologically stable population of activated cells with killer cell properties in spite of a rather constant expression of NK cell immunophenotype.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it is generally agreed that LAK cells morphologically belong to the large granular lymphocyte (LGL) group. The very characteristic two-compartment (specific or lytic) cytoplasmic granules that define LGLs [12] contain perforin and serine esterases (granzymes) [13,14] and are assumed to be involved in cytolytic action by exocytosis of their content [15][16][17]. However, whereas cells intended for adoptive transfer to tumour-bearing animals after having been propagated for 4-5 days in the presence of IL-2 are granular [18], the granules are not present in discernible amounts in their progenitors of isolated spleen cells.…”

Section: Introductionmentioning

confidence: 99%

High Dose IL‐2‐Activated Murine Natural Killer (A‐NK) Cells Accumulate Glycogen and Granules, Lose Cytotoxicity, and Alter Target Cell Interaction In Vitro

et al. 1997

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Activated natural killer (A-NK) cells, defined by immunophenotype and selected by adherence to the plastic, were cultured from murine splenocytes for up to 10 days with the addition of 1000 U/ml of recombinant human IL-2 at 48 h intervals. During culture days 2-4 with high DNA synthesis the initially non-granulated small cells established large granular lymphocyte (LGL) morphology and then differentiated further into giant hypergranulated cells with huge accumulations of glycogen. Timed EM observations indicated that specific dual-compartment (lytic) granules arose by a sequence of events starting with neo-synthesis of small progenitors with a dense core and a few membranous lamellae at one pole. Core and vesicular regions probably expanded independently to give the mature organization of the granule. Eventually, the vesicular region of granules contained large amounts of multi-lamellar material and probable debris, and the dense core could be multiplied. Intracellular proteoglycans, visualized with Cupromeronic Blue cytochemistry, were organized in a three-dimensional network within the dense cores. In contrast with earlier reports, and in spite of several-fold increased granularity, the in vitro cytotoxicity of the A-NK cells against YAC-1 and B16 cells decreased after the third day of culture. A-NK cells with glycogen accumulations caused focal clearing in melanoma monolayers whereas younger effectors adhered to the targets. It is concluded that high dose IL-2 stimulation causes more far-going progressive morphological and functional differentiations of the A-NK cells than has previously been observed with bearing for the use of these cells in experimental adoptive immunotherapy.

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“…DNA fragmentation was analysed by electrophoresis in 1% agarose (Pharmacia) gel as described in [5].…”

Section: Dna Fragmentation Assaymentioning

confidence: 99%

Met‐enkephalin induces cytolytic processes of apoptotic type in K562 human erythroid leukemia cells

et al. 1996

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Cytolytic activity of Met-enke]~halin, an endogenous --17 opioid peptide, was studied within the 10--10 M concentration range in K562 human erythroid leukemia cells. Cytolytic activity was determined by the trypan blue inclusion method after 13, 15 and 18 h of Met-enkephalin co-incubation with target cells. Discrete maxima of cytolytic activity were detected at concentrations of 10-9-10 -1°, 10 -13 and 10 -aS M. Cytolysis was accompanied by internucleosomal DNA fragmentation which is indicative of the mechanism of cell death being apoptosis.

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Ionophore-induced apoptosis: Role of DNA fragmentation and calcium fluxes

Cited by 233 publications

References 42 publications

Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

High Dose IL‐2‐Activated Murine Natural Killer (A‐NK) Cells Accumulate Glycogen and Granules, Lose Cytotoxicity, and Alter Target Cell Interaction In Vitro

Met‐enkephalin induces cytolytic processes of apoptotic type in K562 human erythroid leukemia cells

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