3-Morpholinosydnonimine Hydrochloride Induces p53-Dependent Apoptosis in Murine Primary Neural Cells: A Critical Role for p21ras–MAPK–p19ARF Pathway

Kaji, Tomohiro; Kaieda, Isao; Hisatsune, Tatsuhiro; Kaminogawa, Shuichi

doi:10.1006/niox.2001.0389

Cited by 25 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent studies have been done using isolated proteins inactivated with chemical NO donors. NO-mediated Ras activation has been shown to mediate signal transduction processes in cells including Raf 180 and Erk activation 181,182 leading to many different effects depending on the specific cells 180,[182][183][184][185] . It appears that Ras mutations do not normally occur in human hepatocellular carcinoma development 186 but it is quite clear that the Ras pathway is activated, however as evidenced by significantly enhanced Raf overexpression and enhanced activation 187,188 .…”

Section: Ras Pathway In Cancer Developmentmentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

View full text Add to dashboard Cite

Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

show abstract

Section: Ras Pathway In Cancer Developmentmentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

View full text Add to dashboard Cite

show abstract

“…ARF has been implicated in p53-mediated neuronal death (Kaji et al, 2002). The mechanism by which p53 mediates neuronal death remains to be fully determined, but p53 has been linked to transcriptional activation of pro-apoptotic Bcl-2 family proteins (e.g., Bax) (Miyashita et al, 1994;Sax et al, 2002), and Fas (Kobayashi et al, 1998), although other pathways have been implicated (Morrison and Kinoshita, 2000).…”

Section: Introductionmentioning

confidence: 98%

Expression, interaction, and proteolysis of death‐associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures

et al. 2004

View full text Add to dashboard Cite

Death-associated protein (DAP) kinase is a novel regulator of cell death whose in vivo target(s) and role in neuronal cell death remain uncertain. Since DAP kinase has been implicated in p53-mediated apoptosis, a pathway activated following epileptic brain injury, we examined the relationship between DAP kinase and p53 following seizures. Rats underwent brief (40-min) seizures evoked by intraamygdala kainic acid, which caused the death of ipsilateral CA3 neurons while preserving the contralateral CA3 subfield. Seizures caused a small decline in levels of the approximately 160-kD DAP kinase within injured ipsilateral hippocampus, commensurate with the appearance of an approximately 60-kD fragment, and proteolysis of the p53 inhibitor, murine double minute gene 2 (MDM2). Expression of p53 increased within the ipsilateral hippocampus, and DAP kinase was detected within p53 immunoprecipitates. In contrast, DAP kinase and MDM2 were not proteolyzed within the seizure damage-resistant contralateral hippocampus. Furthermore, DAP kinase and p53 did not interact within the contralateral hippocampus, and p53 cellular localization redistributed from the nucleus to cytoplasm commensurate with p53 proteolysis. These data suggest that DAP kinase may be involved in the p53 pathway during seizure-induced neuronal death.

show abstract

“…Erk (a signaling kinase of cell survival which can be activated by free radicals; [16,17]) and p38 MAPK phosphorylation were examined by Western Blot. Using total Erk or total p38 MAPK as control proteins to ensure equal sample loading, we probed for their phosphorylated forms.…”

Section: Western Blot and Icc Analysis Of Upstream Signaling Pathwaysmentioning

confidence: 99%

“…ONOOquickly combines with CO 2 to form nitrosoperoxycarbonate, which rapidly decomposes to form carbonate radical and nitrogen dioxide, two potently reactive radicals that are believed to be responsible for the deleterious cellular effects of ONOO - [15]. Recent in vitro studies using a donor of NO or ONOO -demonstrated that these molecules could induce apoptosis in murine NSCs or primary neurons through p38 MAP kinase (MAPK) signaling, and p21-MAPK-p19 induced p53 accumulation [16,17]. Correspondingly, activation of caspases and apoptosis in neurons could be blocked by p38 MAPK inhibitors [18].…”

Section: Introductionmentioning

confidence: 99%

Blockade of Peroxynitrite-Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug-Releasing Polymer

Neeley²,

Pritchard³

et al. 2009

Stem Cells

View full text Add to dashboard Cite

Therapeutic impact of neural stem cells (NSCs) for acute spinal cord injury (SCI) has been limited by the rapid loss of donor cells. Neuroinflammation is likely the cause. Since there are close temporal-spatial correlations between the inducible nitric oxide (NO) synthase expression and the donor NSC death after neurotrauma, we reasoned that NO-associated radical species might be the inflammatory effectors which eliminate NSC grafts and kill host neurons. To test this hypothesis, human NSCs (hNSCs: 5×10 4 -2×10 6 /ml) were treated in vitro with "plain" medium, 20 μM glutamate, or donors of NO and peroxynitrite (ONOO -; 100 and 400 μM of spermine or DETA NONOate, and SIN-1, respectively). hNSC apoptosis primarily resulted from SIN-1 treatment, showing ONOO --triggered protein nitration and the activation of p38 MAPK, cytochrome c release, and caspases. Therefore, cell death following post-SCI (p.i.) NO serge may be mediated NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript through conversion of NO into ONOO -. We subsequently examined such causal relationship in a rat model of dual penetrating SCI using a retrievable design of poly-lactic-co-glycolic acid (PLGA) scaffold seeded with hNSCs that was shielded by drug-releasing polymer. Besides confirming the ONOO --induced cell death signaling, we demonstrated that co-transplantation of PLGA film embedded with ONOO -scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or uric acid (1 μmol/film), markedly protected hNSCs 24 h p.i. (total: n = 10). Our findings may provide a bioengineering approach for investigating mechanisms underlying the host microenvironment and donor NSC interaction and help formulate strategies for enhancing graft and host cell survival after SCI.

show abstract

3-Morpholinosydnonimine Hydrochloride Induces p53-Dependent Apoptosis in Murine Primary Neural Cells: A Critical Role for p21ras–MAPK–p19ARF Pathway

Cited by 25 publications

References 35 publications

Nitric Oxide and Cancer Development

Nitric Oxide and Cancer Development

Expression, interaction, and proteolysis of death‐associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures

Blockade of Peroxynitrite-Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug-Releasing Polymer

Contact Info

Product

Resources

About