Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture

Won Ki Kim; Young Sook Pae

doi:10.1016/S0304-3940(96)13011-1

Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture

Won Ki Kim^*
, Young Sook Pae

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

151 Citations (Scopus)

Abstract

The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. D,L-Homocysteine (>300 μM; 16-22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (±)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.

Original language	English
Pages (from-to)	117-120
Number of pages	4
Journal	Neuroscience Letters
Volume	216
Issue number	2
DOIs	https://doi.org/10.1016/S0304-3940(96)13011-1
Publication status	Published - 1996 Sept 27
Externally published	Yes

Keywords

Cerebellar granule cell
Free radical
Homocysteine
Lactate dehydrogenase
N-Methyl-D-aspartate

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0304-3940(96)13011-1

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title = "Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture",

abstract = "The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. D,L-Homocysteine (>300 μM; 16-22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (±)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.",

keywords = "Cerebellar granule cell, Free radical, Homocysteine, Lactate dehydrogenase, N-Methyl-D-aspartate",

author = "Kim, \{Won Ki\} and Pae, \{Young Sook\}",

year = "1996",

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doi = "10.1016/S0304-3940(96)13011-1",

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T1 - Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture

AU - Kim, Won Ki

AU - Pae, Young Sook

PY - 1996/9/27

Y1 - 1996/9/27

N2 - The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. D,L-Homocysteine (>300 μM; 16-22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (±)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.

AB - The present study investigates the possible mechanism responsible for the neurotoxicity of D,L-homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. D,L-Homocysteine (>300 μM; 16-22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N-methyl-D-aspartate (NMDA) antagonist (±)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.

KW - Cerebellar granule cell

KW - Free radical

KW - Homocysteine

KW - Lactate dehydrogenase

KW - N-Methyl-D-aspartate

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U2 - 10.1016/S0304-3940(96)13011-1

DO - 10.1016/S0304-3940(96)13011-1

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C2 - 8904797

AN - SCOPUS:0030604041

SN - 0304-3940

VL - 216

SP - 117

EP - 120

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 2

ER -

Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture

Abstract

Keywords

ASJC Scopus subject areas

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