Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro

Michael Weller; Ann M. Marini; Steven M. Paul

doi:10.1016/0006-8993(92)91043-E

Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro

Michael Weller, Ann M. Marini, Steven M. Paul

Washington University School of Medicine

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

31 Scopus citations

Abstract

3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED₅₀ = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).

Original language	English
Pages (from-to)	160-164
Number of pages	5
Journal	Brain Research
Volume	594
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(92)91043-E
State	Published - Oct 23 1992

Keywords

3-Acetylpyridine
Cerebellar granule cell
Neurotoxicity
Niacinamide

Access to Document

10.1016/0006-8993(92)91043-E

Cite this

@article{f79e36fa3a654db7838f7683e1596f4d,

title = "Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro",

abstract = "3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).",

keywords = "3-Acetylpyridine, Cerebellar granule cell, Neurotoxicity, Niacinamide",

author = "Michael Weller and Marini, {Ann M.} and Paul, {Steven M.}",

year = "1992",

month = oct,

day = "23",

doi = "10.1016/0006-8993(92)91043-E",

language = "English",

volume = "594",

pages = "160--164",

journal = "Brain Research",

issn = "0006-8993",

number = "1",

}

TY - JOUR

T1 - Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro

AU - Weller, Michael

AU - Marini, Ann M.

AU - Paul, Steven M.

PY - 1992/10/23

Y1 - 1992/10/23

N2 - 3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).

AB - 3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).

KW - 3-Acetylpyridine

KW - Cerebellar granule cell

KW - Neurotoxicity

KW - Niacinamide

UR - http://www.scopus.com/inward/record.url?scp=0026463018&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(92)91043-E

DO - 10.1016/0006-8993(92)91043-E

M3 - Article

C2 - 1361407

AN - SCOPUS:0026463018

SN - 0006-8993

VL - 594

SP - 160

EP - 164

JO - Brain Research

JF - Brain Research

IS - 1

ER -

Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this