Nitric Oxide (NO) in Apoptotic versus Necrotic RAW 264.7 Macrophage Cell Death: The Role of NO-Donor Exposure, NAD+Content, and p53 Accumulation

Meßmer, Udo K.; Brüne, Bernhard

doi:10.1006/abbi.1996.0085

Cited by 97 publications

(50 citation statements)

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“…Moreover, inhibitors of poly(ADPribose) polymerase, such as 3-aminobenzamide, were non effective. 24 These experiments ruled out an overlap of apoptotic and necrotic alteration in our studies. However, PARP activation followed by energy depletion has been associated with NO-mediated neurotoxicity 15 and islet cell death.…”

Section: No-evoked Apoptosis: Initial Observationsmentioning

confidence: 76%

Nitric oxide (NO): an effector of apoptosis

1999

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It is appreciated that the production of nitric oxide (NO) from Larginine metabolism is an essential determinate of the innate immune system, important for nonspecific host defense, as well as tumor and pathogen killing. Cytotoxicity as a result of a substantial NO-formation is established to initiate apoptosis, characterized by upregulation of the tumor suppressor p53, changes in the expression of pro-and anti-apoptotic Bcl-2 family members, cytochrome c relocation, activation of caspases, chromatin condensation, and DNA fragmentation. Proof for the involvement of NO was demonstrated by blocking adverse effects by NO-synthase inhibition. However, NOtoxicity is not a constant value and NO may achieve cell protection as well. In part this is understood by transcription and translation of protective proteins, such as cyclooxygenase-2. Alternatively, protection may result as a consequence of a diffusion controlled NO/O 2 7 (superoxide) interaction that redirects the apoptotic initiating activity of NO towards protection. NO is endowed with the unique ability to initiate and to block apoptosis, depending on multiple variables that exist to be elucidated. The crosstalk between cell destructive and protective signaling pathways under the modulatory influence of NO will determine the impact of NO in apoptotic cell death and survival.

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Section: No-evoked Apoptosis: Initial Observationsmentioning

confidence: 76%

Nitric oxide (NO): an effector of apoptosis

1999

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“…On the other hand, inhibition of the electron transport chain of respiration had no effect, 18 and Messmer and Brune 26 showed no reduction in NAD + or ATP levels in NO-induced apoptosis, suggesting that NO does not act through respiratory inhibition. In contrast, others have reported that NO inhibits mitochondrial respiration through two distinct pathways.…”

Section: Proapoptotic Mechanismsmentioning

confidence: 96%

“…25 Therefore, observations using NO donors in murine cells could still be extrapolated to human cells, and may provide useful guidance on the potential therapeutic benefits of using NO in inflammatory conditions. Several NO donors have been demonstrated to elicit apoptosis in RAW 264.7 cells, including sodium nitroprusside (SNP), 26 Snitroso-N-acetylpenicillamine (SNAP), [26][27][28] and the NONOates SPER/NO, 21,22,26,27,29 DEA/NO and DETA/NO. 26 In addition, Sandoval et al 30 demonstrated increased apoptosis in RAW 264.7 cells upon exposure to peroxynitrite (ONOO À ; 100-300 mM over 4 h and 10-100 mM over 14 h).…”

Section: Regulation Of Inflammatory Cell Apoptosis By No Myelomonocytmentioning

confidence: 99%

“…Several NO donors have been demonstrated to elicit apoptosis in RAW 264.7 cells, including sodium nitroprusside (SNP), 26 Snitroso-N-acetylpenicillamine (SNAP), [26][27][28] and the NONOates SPER/NO, 21,22,26,27,29 DEA/NO and DETA/NO. 26 In addition, Sandoval et al 30 demonstrated increased apoptosis in RAW 264.7 cells upon exposure to peroxynitrite (ONOO À ; 100-300 mM over 4 h and 10-100 mM over 14 h). Conversely, Scivittaro et al 27 observed that lower concentrations (30-50 mM) of ONOO À had a protective effect against LPS and IFN-g-induced apoptosis in these cells, although not against exogenous NO-mediated apoptosis.…”

Section: Regulation Of Inflammatory Cell Apoptosis By No Myelomonocytmentioning

confidence: 99%

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Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

et al. 2003

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Apoptosis of inflammatory cells is a critical event in the resolution of inflammation, as failure to undergo this form of cell death leads to increased tissue damage and exacerbation of the inflammatory response. Many factors are able to influence the rate of apoptosis in neutrophils, eosinophils, monocytes and macrophages. Among these is the signalling molecule nitric oxide (NO), which possesses both anti-and proapoptotic properties, depending on the concentration and flux of NO, and also the source from which NO is derived. This review summarises the differential effects of NO on inflammatory cell apoptosis and outlines potential mechanisms that have been proposed to explain such actions.

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“…Our results are in agreement with several other reports that previously demonstrated that exogenous NO induces apoptosis in a macrophage cell line. 14,15,17 In our experiments a fairly large amount of SNP and GSNO was required to induce apoptosis in J774 cells compared to concentration used by other authors in different macrophage cell lines, such as RAW 264.7 16,18,19 or murine peritoneal macrophages. 17,18 However, it has been previously shown that NO-induced apoptosis in J774 macrophages requires high concentration of NO donors, suggesting a lower susceptibility of this cell line to NO.…”

Section: Discussionmentioning

confidence: 81%

Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages

et al. 2001

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We investigated the role of constitutive transcription factor nuclear factor kB (NF-kB) in nitric oxide (NO)-mediated apoptosis in J774 macrophages. Our results show that NFkB is present in untreated J774 cells in a form constitutively active. Incubation of cells with sodium nitroprusside (SNP) and S-nitroso-gluthatione (GSNO), two NO-generating compounds, caused: (a) inhibition of constitutive NF-kB/DNA binding activity; (b) decrease of cell viability; (c) DNA fragmentation; (d) ApopTag positivity. Pyrrolidine dithiocarbamate (PDTC) and N-a-para-tosyl-L-lysine chloromethyl ketone (TLCK), two inhibitors of NF-kB activation, showed the same effects of both NO-generating compounds. Furthermore, SNP and GSNO as well as PDTC and TLCK significantly increased the cytoplasmic level of IkBa. All together these results demonstrate that constitutive NF-kB protects J774 macrophages from NO-induced apoptosis. Moreover, these findings show, for the first time, that NOgenerating compounds may induce apoptosis in J774 macrophages by down-regulating constitutive NF-kB/DNA binding activity and suggest a novel mechanism by which NO induces apoptosis. Cell Death and Differentiation (2001) 8, 144 ± 151.

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Nitric Oxide (NO) in Apoptotic versus Necrotic RAW 264.7 Macrophage Cell Death: The Role of NO-Donor Exposure, NAD+Content, and p53 Accumulation

Cited by 97 publications

References 0 publications

Nitric oxide (NO): an effector of apoptosis

Nitric oxide (NO): an effector of apoptosis

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages

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