Increased vulnerability of neuronal cell lines to sodium nitroprusside- mediated toxicity is caused by the decreased level of nitric oxide metabolites

Chandramallika Ghosh, Debomoy Lahiri

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16 Citations (Scopus)

Abstract

Nitric oxide (NO) is an unstable radical produced during the oxidative deamination catalyzed by NO synthase (NOS) that converts L-arginine to L- citrulline. NO is also generated nonenzymatically from a group of compounds, called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites has been implicated in several disorders, including Alzheimer's disease (AD). Since NO is a highly labile unstable free gas, we measured the stable end products, nitrite and nitrate (NOx). Here, we investigated the effect of SNP-mediated NO release in different cell types and its effect on the beta-amyloid precursor protein (βAPP). When different cell types were induced with SNP, a significant level of NOx was detected in a time and dose-dependent manner over the spontaneous release of NOx by SNP. The astrocytes, glial, and epithelial cell lines released significantly higher level of NOx as compared to neuronal cells following the exposure of SNP. The latter group of cells was more sensitive to NO-mediated cytotoxicity, as demonstrated by the lactate dehydrogenase assay. The SNP- mediated toxicity is known to be caused by the accumulation of cyanide ions and we report that the ability of cells to protect against it depends on the levels of nitric oxide metabolites. Cell lines, such as astrocytic and epithelial, that produce more NOx are better protected against the SNP- induced toxicity than the less NOx-protecting neuronal cell lines. The possibility of differential susceptibility of neurons and astrocytes resulting from the different content of reduced glutathione is also discussed. The release of NOx was prevented by cotreatment with a NO scavenger and superoxide dismutase but not by a NOS inhibitor. The activity of NOS was decreased when cytosolic extracts were incubated with SNP. In the conditioned medium of SNP-induced cells, the level of soluble βAPP (sAPP) was decreased, and this decrease was more apparent in neuronal than astrocytic cell lines. Taken together, these results suggest that the SNP- derived NO release is independent of the NOS pathway, that various cell types metabolize SNP differently, and that neuronal cell lines are more vulnerable with SNP treatment with lowered sAPP secretion. Since the neuronal cell lines lack a nitric-oxide-generated protective mechanism, we speculate that these cells may be the first targets of neurodegeneration by several toxic agents, including the cyanides and peroxynitrites.

Original languageEnglish
Pages (from-to)77-92
Number of pages16
JournalJournal of Molecular Neuroscience
Volume13
Issue number1-2
StatePublished - 1999

Fingerprint

Nitroprusside
Metabolites
Toxicity
Nitric Oxide
Cells
Cell Line
Nitric Oxide Synthase
Amyloid beta-Protein Precursor
Cyanides
Astrocytes
Citrulline
Deamination
Peroxynitrous Acid
Aptitude
Nitric Oxide Donors
Poisons
Cytotoxicity
Conditioned Culture Medium
Nitrites
L-Lactate Dehydrogenase

Keywords

  • Cellular toxicity
  • N1E-115 cells
  • Neurodegeneration
  • PC12 cells
  • Peroxynitrite
  • Superoxide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

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title = "Increased vulnerability of neuronal cell lines to sodium nitroprusside- mediated toxicity is caused by the decreased level of nitric oxide metabolites",
abstract = "Nitric oxide (NO) is an unstable radical produced during the oxidative deamination catalyzed by NO synthase (NOS) that converts L-arginine to L- citrulline. NO is also generated nonenzymatically from a group of compounds, called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites has been implicated in several disorders, including Alzheimer's disease (AD). Since NO is a highly labile unstable free gas, we measured the stable end products, nitrite and nitrate (NOx). Here, we investigated the effect of SNP-mediated NO release in different cell types and its effect on the beta-amyloid precursor protein (βAPP). When different cell types were induced with SNP, a significant level of NOx was detected in a time and dose-dependent manner over the spontaneous release of NOx by SNP. The astrocytes, glial, and epithelial cell lines released significantly higher level of NOx as compared to neuronal cells following the exposure of SNP. The latter group of cells was more sensitive to NO-mediated cytotoxicity, as demonstrated by the lactate dehydrogenase assay. The SNP- mediated toxicity is known to be caused by the accumulation of cyanide ions and we report that the ability of cells to protect against it depends on the levels of nitric oxide metabolites. Cell lines, such as astrocytic and epithelial, that produce more NOx are better protected against the SNP- induced toxicity than the less NOx-protecting neuronal cell lines. The possibility of differential susceptibility of neurons and astrocytes resulting from the different content of reduced glutathione is also discussed. The release of NOx was prevented by cotreatment with a NO scavenger and superoxide dismutase but not by a NOS inhibitor. The activity of NOS was decreased when cytosolic extracts were incubated with SNP. In the conditioned medium of SNP-induced cells, the level of soluble βAPP (sAPP) was decreased, and this decrease was more apparent in neuronal than astrocytic cell lines. Taken together, these results suggest that the SNP- derived NO release is independent of the NOS pathway, that various cell types metabolize SNP differently, and that neuronal cell lines are more vulnerable with SNP treatment with lowered sAPP secretion. Since the neuronal cell lines lack a nitric-oxide-generated protective mechanism, we speculate that these cells may be the first targets of neurodegeneration by several toxic agents, including the cyanides and peroxynitrites.",
keywords = "Cellular toxicity, N1E-115 cells, Neurodegeneration, PC12 cells, Peroxynitrite, Superoxide",
author = "Chandramallika Ghosh and Debomoy Lahiri",
year = "1999",
language = "English",
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journal = "Journal of Molecular Neuroscience",
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TY - JOUR

T1 - Increased vulnerability of neuronal cell lines to sodium nitroprusside- mediated toxicity is caused by the decreased level of nitric oxide metabolites

AU - Ghosh, Chandramallika

AU - Lahiri, Debomoy

PY - 1999

Y1 - 1999

N2 - Nitric oxide (NO) is an unstable radical produced during the oxidative deamination catalyzed by NO synthase (NOS) that converts L-arginine to L- citrulline. NO is also generated nonenzymatically from a group of compounds, called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites has been implicated in several disorders, including Alzheimer's disease (AD). Since NO is a highly labile unstable free gas, we measured the stable end products, nitrite and nitrate (NOx). Here, we investigated the effect of SNP-mediated NO release in different cell types and its effect on the beta-amyloid precursor protein (βAPP). When different cell types were induced with SNP, a significant level of NOx was detected in a time and dose-dependent manner over the spontaneous release of NOx by SNP. The astrocytes, glial, and epithelial cell lines released significantly higher level of NOx as compared to neuronal cells following the exposure of SNP. The latter group of cells was more sensitive to NO-mediated cytotoxicity, as demonstrated by the lactate dehydrogenase assay. The SNP- mediated toxicity is known to be caused by the accumulation of cyanide ions and we report that the ability of cells to protect against it depends on the levels of nitric oxide metabolites. Cell lines, such as astrocytic and epithelial, that produce more NOx are better protected against the SNP- induced toxicity than the less NOx-protecting neuronal cell lines. The possibility of differential susceptibility of neurons and astrocytes resulting from the different content of reduced glutathione is also discussed. The release of NOx was prevented by cotreatment with a NO scavenger and superoxide dismutase but not by a NOS inhibitor. The activity of NOS was decreased when cytosolic extracts were incubated with SNP. In the conditioned medium of SNP-induced cells, the level of soluble βAPP (sAPP) was decreased, and this decrease was more apparent in neuronal than astrocytic cell lines. Taken together, these results suggest that the SNP- derived NO release is independent of the NOS pathway, that various cell types metabolize SNP differently, and that neuronal cell lines are more vulnerable with SNP treatment with lowered sAPP secretion. Since the neuronal cell lines lack a nitric-oxide-generated protective mechanism, we speculate that these cells may be the first targets of neurodegeneration by several toxic agents, including the cyanides and peroxynitrites.

AB - Nitric oxide (NO) is an unstable radical produced during the oxidative deamination catalyzed by NO synthase (NOS) that converts L-arginine to L- citrulline. NO is also generated nonenzymatically from a group of compounds, called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites has been implicated in several disorders, including Alzheimer's disease (AD). Since NO is a highly labile unstable free gas, we measured the stable end products, nitrite and nitrate (NOx). Here, we investigated the effect of SNP-mediated NO release in different cell types and its effect on the beta-amyloid precursor protein (βAPP). When different cell types were induced with SNP, a significant level of NOx was detected in a time and dose-dependent manner over the spontaneous release of NOx by SNP. The astrocytes, glial, and epithelial cell lines released significantly higher level of NOx as compared to neuronal cells following the exposure of SNP. The latter group of cells was more sensitive to NO-mediated cytotoxicity, as demonstrated by the lactate dehydrogenase assay. The SNP- mediated toxicity is known to be caused by the accumulation of cyanide ions and we report that the ability of cells to protect against it depends on the levels of nitric oxide metabolites. Cell lines, such as astrocytic and epithelial, that produce more NOx are better protected against the SNP- induced toxicity than the less NOx-protecting neuronal cell lines. The possibility of differential susceptibility of neurons and astrocytes resulting from the different content of reduced glutathione is also discussed. The release of NOx was prevented by cotreatment with a NO scavenger and superoxide dismutase but not by a NOS inhibitor. The activity of NOS was decreased when cytosolic extracts were incubated with SNP. In the conditioned medium of SNP-induced cells, the level of soluble βAPP (sAPP) was decreased, and this decrease was more apparent in neuronal than astrocytic cell lines. Taken together, these results suggest that the SNP- derived NO release is independent of the NOS pathway, that various cell types metabolize SNP differently, and that neuronal cell lines are more vulnerable with SNP treatment with lowered sAPP secretion. Since the neuronal cell lines lack a nitric-oxide-generated protective mechanism, we speculate that these cells may be the first targets of neurodegeneration by several toxic agents, including the cyanides and peroxynitrites.

KW - Cellular toxicity

KW - N1E-115 cells

KW - Neurodegeneration

KW - PC12 cells

KW - Peroxynitrite

KW - Superoxide

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