Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

Ortíz-Ortíz, Miguel A.; Morán, José M.; González‐Polo, Rosa A.; Niso-Santano, Mireia; Soler, Germán; Pedro, José Manuel Bravo-San; Fuentes, José

doi:10.1007/s12640-009-9065-6

Cited by 29 publications

(16 citation statements)

References 39 publications

(40 reference statements)

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“…Human lung epithelial cells treated with PQ also express significant amounts of iNOS mRNA [23]. Similarly, human-derived cell lines such as A549 lung carcinoma [26] or the human neuroblastoma-derived cell line SH-SY5Y [27] show upregulation of iNOS expression after PQ exposure.…”

Section: Paraquat and Nitric Oxide Synthasesmentioning

confidence: 99%

“…These studies implicitly assumed that the detected NOS activity was due to nNOS. Although changes in NOS activity have not been established after PQ exposure in rodents either in vivo or in vitro [32][33][34], the rationale for this assumption was that human neuroblastoma cells exposed to PQ do not show modulation of the expression of nNOS [27], thus supporting the conclusion that PQ does not regulate the expression of this isoenzyme.…”

Section: An Increase Of Omentioning

confidence: 99%

“…In biological systems, this attack leads to modification of tyrosine residues to produce 3-nitrotyrosine. The formation of 3-nitrotyrosine can be thought of as a stable biological marker for the formation of ONOO − [11,27,45,46] because the formation of 3-nitrotyrosine is usually not induced by ROS [47]; rather, it is caused by ONOO − or other reactive nitrogen species (RNS). Formation of 3-nitrotyrosine has been shown in rat liver tissue 3 h after the administration of a lethal dose of PQ [22], in the substantia nigra after 3 weeks of PQ treatment [48], and in human neuroblastoma cells after 24 h of PQ exposure [27].…”

Section: Role Of No In Pq-mediated Toxicity: Is It Beneficial or Harmmentioning

confidence: 99%

“…The formation of 3-nitrotyrosine can be thought of as a stable biological marker for the formation of ONOO − [11,27,45,46] because the formation of 3-nitrotyrosine is usually not induced by ROS [47]; rather, it is caused by ONOO − or other reactive nitrogen species (RNS). Formation of 3-nitrotyrosine has been shown in rat liver tissue 3 h after the administration of a lethal dose of PQ [22], in the substantia nigra after 3 weeks of PQ treatment [48], and in human neuroblastoma cells after 24 h of PQ exposure [27]. In contrast, one study found that exposure of mouse hippocampal neuronal cells for 6 h to a single administration of PQ did not modulate the formation of 3-nitrotyrosine [49], and another study found that RAW 264.7 macrophages exposed to PQ showed a decreased ratio of 3-nitrotyrosine formation [11].…”

Section: Role Of No In Pq-mediated Toxicity: Is It Beneficial or Harmmentioning

confidence: 99%

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Nitric oxide in paraquat‐mediated toxicity: A review

Morán

Ortíz-Ortíz

Ruiz-Mesa

et al. 2010

J Biochem & Molecular Tox

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Paraquat, a cationic herbicide, produces degenerative lesions in the lung and in the nervous system after systemic administration to man and animals. Many cases of acute poisoning and death have been reported over the past few decades. Although a definitive mechanism of toxicity of paraquat has not been delineated, a cyclic single electron reduction/oxidation is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: the generation of the superoxide anion, which can lead to the formation of more toxic reactive oxygen species which are highly reactive to cellular macromolecules; and the oxidation of reducing equivalents (e.g., NADPH, reduced glutathione), which results in the disruption of important NADPH-requiring biochemical processes necessary for normal cell function. Nitric oxide is an important signaling molecule that reacts with superoxide derived from the paraquat redox cycle, to form the potent oxidant peroxynitrite, which causes serious cell damage. Although nitric oxide has been involved in the mechanism of paraquat-mediated toxicity, the role of nitric oxide has been controversial as both protective and harmful effects have been described. The present review summarizes recent findings in the field and describes new knowledge on the role of nitric oxide in the paraquat-mediated toxicity.

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Section: Paraquat and Nitric Oxide Synthasesmentioning

confidence: 99%

Section: An Increase Of Omentioning

confidence: 99%

Section: Role Of No In Pq-mediated Toxicity: Is It Beneficial or Harmmentioning

confidence: 99%

Section: Role Of No In Pq-mediated Toxicity: Is It Beneficial or Harmmentioning

confidence: 99%

See 2 more Smart Citations

Nitric oxide in paraquat‐mediated toxicity: A review

Morán

Ortíz-Ortíz

Ruiz-Mesa

et al. 2010

J Biochem & Molecular Tox

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“…Under specific conditions, however, NO and its metabolites become neurotoxic [18,19]. In addition, a recent study suggests that NO mediates toxicity in paraquat-exposed SH-SY5Y cells and that 7-nitroindazole exerts a protective role [20].…”

Section: No and Its Physiologic Rolementioning

confidence: 99%

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

Lahiri

Ghosh

Rogers

et al. 2010

Aging and Age-Related Disorders

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Role of nitric oxide in neurodegeneration and vulnerability of neuronal cells to nitric oxide metabolites and reactive oxygen species NO can also be released chemically from a group of compounds called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites is believed to be involved in several disorders, including Alzheimer's disease (AD). This chapter summarizes the role of NO and oxidative stress in neurodegeneration and describes the experimental evidence of increased vulnerability of neuronal cells to NO metabolites and other reactive oxygen species (ROS). As NO is a highly labile, unstable free gas, levels of the stable end products, such as nitrite and nitrate (NOx), were measured. When different cell types were treated with SNP, a significant level of NOx was detected in a time-and dose-dependent manner, which was more than the spontaneous release by SNP. Astrocytic, glial, and epithelial cell lines released significantly higher levels of NOx compared with neuronal cell lines after SNP treatment. Neuronal cells were more sensitive to SNP-induced cytotoxicity, as determined by lactate dehydrogenase assay. SNP-mediated toxicity is known to be due, in large part, to the accumulation of cyanide ions, and the ability of cells to protect themselves against this toxicity depends upon their levels of NO metabolites. Cell lines that generate more NOx, such as astrocytic and epithelial, are better protected against the SNP-induced toxicity than are less NOx-protecting neuronal cell lines. Our results suggest that various cell types metabolize SNP differently and that neuronal cell lines are more vulnerable than other cell types to SNP treatment. As neuronal cell lines lack an NO-generated protective mechanism, these cells are potentially primary targets for neurodegeneration by toxic agents including the free radicals and peroxynitrites.

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Interferon Gamma Potentiates the Injury Caused by MPP(+) on SH-SY5Y Cells, Which is Attenuated by the Nitric Oxide Synthases Inhibition

et al. 2014

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This study examined whether the cytokine interferon (IFN) gamma plays a role in the injury of SH-SY5Y cells caused by MPP(+) (1-methyl-4-phenylpyridinium). First of all, IFN-gamma sensitized cells to the neurotoxin MPP(+), as determined by MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide) assay. MPP(+)-injured cells showed higher reactive oxygen species (ROS) levels, which was reinforced by IFN-gamma. The injury triggered a marked expression of the neuronal NOS (nNOS) enzyme. L-NAME [N(ω)-nitro-L-arginine methyl ester, a non-specific NOS inhibitor] reestablished the cell viability after IFN-gamma challenging, and recovered cells from MPP(+) injury (95.0 vs. 84.7 %; P < 0.05). Seven-NI (7-nitroindazole, a nNOS inhibitor) protected cells against the injury by MPP(+) co-administered with IFN-gamma. Both inhibitors restrained the apoptosis of SH-SY5Y cells caused by MPP(+)/IFN-gamma. Regarding oxidative stress, L-NAME and 7-NI attenuated the increase in ROS levels caused by MPP(+) (45.3 or 48.4 vs. 87.9 %, P < 0.05). Indeed, L-NAME was more effective than 7-NI for reducing oxidative stress caused by MPP(+) under IFN-gamma exposition. The nNOS gene silencing by small-interfering RNAs recovered cells challenged by IFN-gamma (24 h), or MPP(+) (8 h). In conclusion, IFN-gamma sensitizes cells to MPP(+)-induced injury, also causing an increase in ROS levels. Pretreating cells with L-NAME or 7-NI reverts both the oxidative stress and apoptosis triggered by the neurotoxin MPP(+). Taking together, our data reinforce that IFN-gamma and NOS enzymes play a role in oxidative stress and dopaminergic cell death triggered by MPP(+).

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Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

Cited by 29 publications

References 39 publications

Nitric oxide in paraquat‐mediated toxicity: A review

Nitric oxide in paraquat‐mediated toxicity: A review

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

Interferon Gamma Potentiates the Injury Caused by MPP(+) on SH-SY5Y Cells, Which is Attenuated by the Nitric Oxide Synthases Inhibition

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