S-nitrosation ameliorates homocysteine-mediated neurotoxicity in primary culture of rat cortical neurons

Research output: Contribution to journalArticle

Abstract

The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF)), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine (>1 mM) resulted in a significant neuronal cell death. At comparable concentrations (<10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteine partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalKorean Journal of Pharmacology
Volume32
Issue number2
Publication statusPublished - 1996 Nov 6
Externally publishedYes

Fingerprint

Nitrosation
Homocysteine
Neurons
N-Methylaspartate
Sulfhydryl Compounds
Nitric Oxide
Cell Death
S-Nitrosothiols
Endothelium-Dependent Relaxing Factors
Blood Vessels
Atherosclerosis
Thrombosis
Stroke
Calcium
Brain
S-nitrosohomocysteine

Keywords

  • calcium
  • cortical neuron
  • homocysteine
  • neurotoxicity
  • primary culture
  • S-nitrosohomocysteine

ASJC Scopus subject areas

  • Pharmacology

Cite this

S-nitrosation ameliorates homocysteine-mediated neurotoxicity in primary culture of rat cortical neurons. / Kim, Won-Ki.

In: Korean Journal of Pharmacology, Vol. 32, No. 2, 06.11.1996, p. 169-175.

Research output: Contribution to journalArticle

@article{9f54a1cd011749958cd2081d9d70d851,
title = "S-nitrosation ameliorates homocysteine-mediated neurotoxicity in primary culture of rat cortical neurons",
abstract = "The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF)), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine (>1 mM) resulted in a significant neuronal cell death. At comparable concentrations (<10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteine partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.",
keywords = "calcium, cortical neuron, homocysteine, neurotoxicity, primary culture, S-nitrosohomocysteine",
author = "Won-Ki Kim",
year = "1996",
month = "11",
day = "6",
language = "English",
volume = "32",
pages = "169--175",
journal = "Korean Journal of Physiology and Pharmacology",
issn = "1226-4512",
publisher = "Korean Physiological Soc. and Korean Soc. of Pharmacology",
number = "2",

}

TY - JOUR

T1 - S-nitrosation ameliorates homocysteine-mediated neurotoxicity in primary culture of rat cortical neurons

AU - Kim, Won-Ki

PY - 1996/11/6

Y1 - 1996/11/6

N2 - The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF)), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine (>1 mM) resulted in a significant neuronal cell death. At comparable concentrations (<10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteine partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.

AB - The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF)), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine (>1 mM) resulted in a significant neuronal cell death. At comparable concentrations (<10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteine partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.

KW - calcium

KW - cortical neuron

KW - homocysteine

KW - neurotoxicity

KW - primary culture

KW - S-nitrosohomocysteine

UR - http://www.scopus.com/inward/record.url?scp=0029912804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029912804&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0029912804

VL - 32

SP - 169

EP - 175

JO - Korean Journal of Physiology and Pharmacology

JF - Korean Journal of Physiology and Pharmacology

SN - 1226-4512

IS - 2

ER -