Low-Dose Gamma Irradiation Enhances Superoxide Anion Production by Nonirradiated Cells Through TGF-β1-Dependent Bystander Signaling

Temme, Jennifer; Bauer, Georg

doi:10.1667/rr3161.2

Cited by 51 publications

(42 citation statements)

References 131 publications

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“…The effect of treatment with siTGFβ1, but not that with siTGFβR was completely abrogated through addition of exogenous TGFβ1 (p<0.001) ( Figure 3A Quantitative and functional aspects of NOX1-dependent superoxide anion generation. A recently described functional assay allowed quantification of the relative concentration of extracellular superoxide anions (27). It is based on the bellshaped inhibition curve of superoxide anion-dependent signaling by Cu/Zn SOD.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, transformed cells such as 208FSrc3 cells seem to produce less TGFβ1 and therefore require supplementation with exogenous TGFβ1 under experimental conditions. Based on our analysis, TGFβ1 seems to have two central targets in this context: it seems to control the activity of NOX1 (27) and to drive the release of the peroxidase domain of DUOX that is split from DUOX by the action of MMP (28). The strong inhibitory effect of knockdown of PKCzeta is in line with these findings, as PKC zeta is involved in the control of NOX1 (31) and a partial dependence of DUOX-coded POD release on PKC zeta was directly demonstrated here.…”

Section: Autocrine Apoptosis Induction In Neuroblastoma Cells Dependsmentioning

confidence: 88%

“…Without addition of TGFβ1, the kinetics is delayed (9). This finding is explained by the stimulatory role of TGFβ1 on NOX1 activity (27) and on peroxidase release (28). As apoptosis induction in transformed cells was abrogated through siRNA-based knockdown of NOX1 and DUOX1, whereas knockdown of iNOS had no inhibitory effect, it seemed to be exclusively due to HOCl signaling.…”

Section: Discussionmentioning

confidence: 99%

“…After 4 h of incubation at 37˚C in 5% CO 2 , the percentage of apoptotic cells was determined by inverted phasecontrast microscopy as described above. This specific feature of the action of Cu/Zn-SOD with its characteristic curve facilitates the relative quantification of the extracellular superoxide anion concentration (26,27), as there is a linear relationship between superoxide anion concentration and SOD required for optimal inhibition. As SOD does not penetrate the cells, only extracellular superoxide anions are determined.…”

Section: Small Interfering Ribonucleic Acid (Sirna)-based Analysis mentioning

confidence: 99%

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Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in Malignant Cells

Bauer

2017

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Abstract. Intercellular reactive oxygen/reactive nitrogen species-(ROS/RNS)-dependent induction of apoptosis in malignant cells is discussed as a potential control step during oncogenesis. In previous studies, the mechanism of intercellular apoptosis-inducing signaling was mainly established throughSelective induction of apoptosis in transformed cells is established either through their interaction with neighboring non-transformed cells or through autocrine apoptotic selfdestruction (1-3). Thereby, the HOCl (2, 5) and the nitric oxide/peroxynitrite (NO/PON) signaling pathways (2, 5, 6) are the dominant intercellular apoptosis-inducing signaling pathways [reviewed in (5)]. Both pathways are driven by superoxide anions which are generated by membraneassociated NADPH oxidase-1 (NOX1) of malignant cells (4, 7) and result in the generation of hydroxyl radicals that induce apoptosis through lipid peroxidation in the cell membrane (8).Mechanisms and the multiple modes of interaction of these pathways have been elucidated through inhibitor and reconstitution experiments [reviewed in (4, 5, 9)].Elimination of transformed cells through selective apoptosis induction mediated by intercellular reactive oxygen species (ROS)-dependent signaling has been discussed as a potential natural tumor-preventive mechanism (4, 10, 11). This concept is in agreement with the pioneering work of Deichman et al. , who have shown that tumor progression requires establishment of resistance to H 2 O 2 (12, 13). Resistance is achieved through the expression of membraneassociated catalase (8,14,15). Catalase interferes with the HOCl signaling pathway through decomposition of H 2 O 2 and with NO/PON signaling through oxidation of NO and decomposition of PON (5,8,16,17). Recent quantitative characterization of membrane-associated catalase has shown that localization of catalase on the outside of cells is already associated with the transformed state of the cells, however, at a concentration that is not sufficient to prevent intercellular ROS-dependent signaling (15). Catalase seems to be released by tumor cells and is covalently attached to the cells through the action of transglutaminase-2 (15).In addition to membrane-associated catalase, tumor cells also carry superoxide dismutase (SOD) on their membrane. SOD has a co-modulatory role through preventing superoxide anion-dependent inhibition of catalase (9, 18).The functional complex of membrane-associated NOX1 and protective catalase and SOD represents a regular characteristic of tumor cells and therefore is a focus for the establishment of novel therapeutic approaches (18)(19)(20). The complex signaling chemistry of transformed cells, or tumor cells after inhibition of their membrane-associated catalase, has, so far, been mainly elucidated through inhibitor studies and reconstitution experiments. Small interfering ribonucleic acid (siRNA)-based knockdown of defined 499

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Section: Resultsmentioning

confidence: 99%

Section: Autocrine Apoptosis Induction In Neuroblastoma Cells Dependsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Small Interfering Ribonucleic Acid (Sirna)-based Analysis mentioning

confidence: 99%

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Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in Malignant Cells

Bauer

2017

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“…Knockdown of NOX1 was found to be 94% following the protocol described recently (22). After knockdown of iNOS, NOdependent effects were undetectable.…”

Section: Methodsmentioning

confidence: 99%

The Antitumor Effect of Single-domain Antibodies Directed Towards Membrane-associated Catalase and Superoxide Dismutase

Bauer

Motz²

2016

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Key Roles of Reactive Oxygen and Nitrogen Species

Graves

Bauer

2018

Comprehensive Clinical Plasma Medicine

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Low-Dose Gamma Irradiation Enhances Superoxide Anion Production by Nonirradiated Cells Through TGF-β1-Dependent Bystander Signaling

Cited by 51 publications

References 131 publications

Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in Malignant Cells

Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in Malignant Cells

The Antitumor Effect of Single-domain Antibodies Directed Towards Membrane-associated Catalase and Superoxide Dismutase

Key Roles of Reactive Oxygen and Nitrogen Species

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