Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

Grusch, Michael; Polgar, Doris; Gfatter, S; Leuhuber, Katharina; Huettenbrenner, S; Leisser, Christina; Fuhrmann, G; Kassie, Fekadu; Steinkellner, Hans; Smid, Kees; Peters, Godefridus J.; Jayaram, Hiremagalur N.; Klepal, Waltraud; Szekeres, Thomas; Knasmüller, Siegfried; Krupitza, Georg

doi:10.1038/sj.cdd.4400937

Cited by 69 publications

(25 citation statements)

References 47 publications

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“…Apoptosis is an energy-requiring process (45)(46)(47)(48)(49). Indeed, the presence or absence of ATP has a profound effect on whether the cell will die by apoptosis or necrosis (48).…”

Section: Discussionmentioning

confidence: 99%

Endotoxin Inhibits Apoptosis but Induces Primary Necrosis in Neutrophils

et al. 2005

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Lipopolysaccharide (LPS) is known to prolong the functional lifespan of neutrophils at a site of infection by preventing apoptosis through inhibitor of apoptosis proteins (IAPs). We hypothesized that the increased neutrophil lifespan ultimately leads to a larger fraction of cells undergoing uncontrolled, primary necrosis. Diluted venous whole blood was incubated with increasing concentrations of LPS for up to 36 hr. The percentages of apoptotic, necrotic and viable neutrophils were assessed using the Annexin V/propidium iodide flow cytometric assay. LPS led to a reduction of neutrophil apoptosis and increased the number of viable cells at 12, 24, and 36 hr of incubation. At the same time intervals, there was a significant increase in the percentage of cells undergoing primary necrosis for all concentrations of LPS (e.g., 10 ng/ml LPS at 24 h produced a mean increase from 9.6% in controls to 30.6%, p < 0.001). This increase in direct neutrophil necrosis following LPS activation may amplify local proinflammatory effects through less well controlled release of neutrophil contents into surrounding tissue.

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“…Apoptosis is an energy-requiring process (45)(46)(47)(48)(49). Indeed, the presence or absence of ATP has a profound effect on whether the cell will die by apoptosis or necrosis (48).…”

Section: Discussionmentioning

confidence: 99%

Endotoxin Inhibits Apoptosis but Induces Primary Necrosis in Neutrophils

et al. 2005

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“…Any modification of the structure of AAI, namely the addition, deletion, substitution, or replacement of these side chains drastically reduces toxicity. In AAII, the removal of the ''methoxy'' group from its position reduces the toxicity of AAII, a compound that differs from AAI by one ''methoxy'' group [17]. Therefore, specificity of AA and its activity are dependent on the chemical structure and conformation of particular AA specie as well as on the intracellular environment in specific tissue.…”

Section: Discussionmentioning

confidence: 98%

“…The morphological criteria defining the cell death type upon staining were as follows: the nuclei of viable cells stain blue (the cytoplasm remains invisible); apoptotic cells can be recognized by condensed chromatin, which usually stained more intensely blue; a similar chromatin condensation is observed at the late stage of apoptosis, but the color shifts to pink due to PI intrusion through leaky membranes; pink colored nuclei without chromatin condensation are typical of necrotic cells [17]. Using this approach, we found that most of the nonapoptotic dead cells were necrotic.…”

Section: Aai Inhibits Gdh Activity In Proximal Tubule Cellsmentioning

confidence: 99%

“…To analyze mode of cell death cells we stained cells with membrane permeable Hoechst 33342 (excitation wavelength, 348 nm; emission wavelength, 479 nm) along or together with DNA dye PI (excitation wavelength, 500 nm; emission wavelength, 640 nm) generally as described [17]. Briefly: cells were grown on 18 mm cover slips.…”

Section: Hoechst 33342 and Propidium Iodide (Pi) Stainingmentioning

confidence: 99%

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Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in renal tubular epithelial cells

et al. 2011

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Ingestion of aristolochic acids (AA) contained in herbal remedies results in a renal disease and, frequently, urothelial malignancy. The genotoxicity of AA in renal cells, including mutagenic DNA adduct formation, is well-documented. However, the mechanisms of AA-induced tubular atrophy and renal fibrosis are largely unknown. Epithelial cell death is a critical characteristic of these pathological conditions. To elucidate the mechanisms of AA-induced cytotoxicity, we explored AA-interacting proteins in tubular epithelial cells (TEC). We found that AA interacts with a mitochondrial enzyme glutamate dehydrogenase (GDH) and moderately inhibits its activity. We report that AA induces cell death in GDH-knockdown TEC preferentially via non-apoptotic means, whereas in GDH-positive cells, death was executed by both the non-apoptotic and apoptotic mechanisms. Apoptosis is an energy-reliant process and demands higher adenosine 5'-triphosphate (ATP) consumption than does the non-apoptotic cell death. We found that, after AAI treatment, the ATP depletion is more pronounced in GDH-knockdown cells. When we reduced ATP in TEC cells by inhibition of glycolysis and mitochondrial respiration, cell death mode switched from apoptosis and necrosis to necrosis only. In addition, in cells incubated at low glucose and no glutamine conditions, oxaloacetate and pyruvate reduced AAI-induced apoptosis our data suggest that AAI-GDH interactions in TEC are critical for the induction of apoptosis by direct inhibition of GDH activity. AA binding may also induce changes in GDH conformation and promote interactions with other molecules or impair signaling by GDH metabolic products, leading to apoptosis.

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“…Depletion of intracellular energy supply has been shown to switch apoptosis to necrosis [14]. Conversely, maintenance of the energy supply favors cell death by apoptosis [15].…”

Section: Introductionmentioning

confidence: 99%

Delayed mitochondrial dysfunction in apoptotic hair cells in chinchilla cochleae following exposure to impulse noise

2007

Apoptosis

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Apoptotic death of hair cells (HCs) in the cochlea has been found following exposure to intense noise. The current study was designed to examine the mitochondrial energetic function of HCs during the course of noise-induced apoptosis. Two aspects of the mitochondrial energetic function, succinate dehydrogenase (SDH) activity and mitochondrial membrane potential (MMP), were examined in HCs of chinchilla cochleae following exposure to a series of 75 pairs of impulse noises at 155 dB pSPL. The results showed that nuclear condensation and uptake of propidium iodide or trypan blue appeared at 10 min after the noise exposure, indicating a rapid progression of HC apoptosis. However, SDH activity was preserved at this time point. As the time elapsed (1 hr or 24 hrs) after the noise exposure, all newly-generated apoptotic HCs showed strong SDH activity, indicating the preservation of SDH activity during the course of apoptosis. Examination of MMP with rhodamine 123 staining revealed that MMP was sustained in the apoptotic HCs having mild nuclear condensation, even after the occurrence of cell membrane leakage. MMP was reduced with further progression of nuclear condensation. These results suggest the presence of a delayed mitochondrial dysfunction in apoptotic HCs following exposure to intense noise.

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Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

Cited by 69 publications

References 47 publications

Endotoxin Inhibits Apoptosis but Induces Primary Necrosis in Neutrophils

Endotoxin Inhibits Apoptosis but Induces Primary Necrosis in Neutrophils

Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in renal tubular epithelial cells

Delayed mitochondrial dysfunction in apoptotic hair cells in chinchilla cochleae following exposure to impulse noise

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