Nitric Oxide Production and Mitochondrial Dysfunction during Rat Thymocyte Apoptosis

Bustamante, Juanita; Bersier, Geraldine; Romero, M. Soledad; Badin, Romina Aron; Boveris, Alberto

doi:10.1006/abbi.2000.1716

Cited by 52 publications

(26 citation statements)

References 40 publications

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“…Several proapoptotic stimuli including tumor necrosis factor ␣ (45) and IL-1␤ (46) have been shown to require synthesis of NO to exert their apoptotic effect. Furthermore, it recently has been reported that mitochondrial membranes generate NO after treatment with different apoptotic stimuli and that this correlates with mitochondrial respiratory impairment as an early phenomenon of apoptosis (47). Moreover, in Jurkat cells an elevation of ⌬ m after Fas signaling has been reported and interpreted as the initiation of the apoptotic program (48).…”

Section: Discussionmentioning

confidence: 98%

The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death

Beltrán

Mathur²,

Duchen³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

360

257

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The mitochondrion is a key organelle in the control of cell death. Nitric oxide (NO) inhibits complex IV in the respiratory chain and is reported to possess both proapoptotic and antiapoptotic actions. We investigated the effects of continuous inhibition of respiration by NO on mitochondrial energy status and cell viability. Serum-deprived human T cell leukemia (Jurkat) cells were exposed to NO at a concentration that caused continuous and complete (ϳ85%) inhibition of respiration. Serum deprivation caused progressive loss of mitochondrial membrane potential (⌬ m) and apoptotic cell death. In the presence of NO, ⌬m was maintained compared to controls, and cells were protected from apoptosis. Similar results were obtained by using staurosporin as the apoptotic stimulus. As exposure of serum-deprived cells to NO progressed (>5 h), however, ⌬m fell, correlating with the appearance of early apoptotic features and a decrease in cell viability. Glucose deprivation or iodoacetate treatment of cells in the presence of NO resulted in a collapse of ⌬m, demonstrating involvement of glycolytic ATP in its maintenance. Under these conditions cell viability also was decreased. Treatment with oligomycin and͞or bongkrekic acid indicated that the maintenance of ⌬ m during exposure to NO is caused by reversal of the ATP synthase and other electrogenic pumps. Thus, blockade of complex IV by NO initiates a protective action in the mitochondrion to maintain ⌬m; this results in prevention of apoptosis. It is likely that during cellular stress involving increased generation of NO this compound will trigger a similar sequence of events, depending on its concentration and duration of release. mitochondrial membrane potential ͉ apoptosis ͉ necrosis

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Section: Discussionmentioning

confidence: 98%

The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death

Beltrán

Mathur²,

Duchen³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

360

257

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“…reactive oxygen species, ROS; Madeo et al, 1999;Bustamante et al, 2000) and internal processes (e.g. replication failures or developmental programmed cell death; Okuno et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype

Mousavi

Robson

2004

Microbiology

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When protoplasts of the opportunistic fungal pathogen Aspergillus fumigatus were treated with low but toxic levels of hydrogen peroxide (0?1 mM) or amphotericin B (0?5 mg ml "1 ), loss of cell viability and death were associated with a number of phenotypic changes characteristic of apoptosis. The percentage of protoplasts staining positive with annexin V-FITC, an indicator of the externalization of phosphatidylserine and an early marker of apoptosis, rose to~55 % within 1 h. This was followed by a similar increase in apoptotic DNA fragmentation detected by the TUNEL assay, and led to a loss of cell permeability and death in~90 % of protoplasts, as indicated by the uptake of propidium iodide. The development of an apoptotic phenotype was blocked when protoplasts were pre-treated with the protein synthesis inhibitor cycloheximide, indicating active participation of the cell in the process. However, no significant activity against synthetic caspase substrates was detected, and the inclusion of the cell-permeant broad-spectrum caspase inhibitor Z-VAD-fmk did not block the development of the apoptotic-like phenotype. Higher concentrations of H 2 O 2 (1?8 mM) and amphotericin B (1 mg ml "1 ) caused protoplasts to die without inducing an apoptotic phenotype. As predicted, the fungistatic antifungal agent itraconazole, which inhibits growth without causing immediate cell death, did not induce an apoptotic-like phenotype. INTRODUCTIONThe incidence of life-threatening invasive aspergillosis in immunocompromised hosts has increased dramatically over the last two decades (Groll et al., 1996;Vogeser et al., 1997;Latgé, 1999;Denning et al., 2002). Aspergillus fumigatus is the most common aetiological agent of invasive aspergillosis, being responsible for approximately 90 % of human infections (Derouin, 1994). The incidence of invasive aspergillosis varies between 1 and 19 % for patients who have undergone solid organ transplantation (Patel & Paya, 1997;Verweij & Denning, 1997), and patients with leukaemia, AIDS and granulomatous disease are also at risk (Brown et al., 1998;Denning, 1998;Kaizer et al., 1998). In contrast, the disease is rarely found in immunocompetent hosts (Karim et al., 1997). A. fumigatus is a common, widespread saprophytic fungus, and environmental surveys indicate that humans inhale several hundred A. fumigatus conidia per day (Hospenthal et al., 1998). Ingestion and killing of spores by alveolar macrophages represent the first line of defence against infection, mainly by non-oxidative mechanisms, whilst neutrophils employ an oxidative respiratory burst to kill germinating conidia that have escaped macrophage engulfment (Schaffner et al., 1986;Levitz et al., 1986; Morgenstern et al., 1997;Roilides et al., 1998; Latgé, 2001). Invasive aspergillosis has a high mortality and morbidity rate, with only 34 % of patients showing a favourable response to antifungal therapy (Denning, 1996). The fungicidal agent amphotericin B is widely used to treat invasive aspergillosis, although it can have serious side-effect...

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“…Immune system-related NOS is an inducible and calcium-independent enzyme that produces NO in sufficient quantities to cause deleterious effects to several pathogenic agents (Simmons and Murphy, 1992;Magalhaes et al, 2006). In addition, new isoforms or mitochondrial variants of NOS (mtNOS) have since been described in rat liver (Ghafourifar and Richter, 1997;Giulivi et al, 1998), thymus (Bustamante et al, 2000), and brain (Riobo et al, 2002). mtNOS is bound to mitochondrial cytochrome c oxidase (COX) (Persichini et al, 2005) and to complex I (Franco et al, 2006), thus favoring a steric relationship between the released NO and the control of respiration.…”

Section: No Production In Mammalian and Plant Cellsmentioning

confidence: 99%

Nitric oxide: promoter or suppressor of programmed cell death?

et al. 2010

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Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent andindependent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.

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Nitric Oxide Production and Mitochondrial Dysfunction during Rat Thymocyte Apoptosis

Cited by 52 publications

References 40 publications

The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death

The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death

Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype

Nitric oxide: promoter or suppressor of programmed cell death?

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