U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells

Susan M. Sparrow, Jodi Carter, Neale D. Ridgway, Harold W. Cook, David M. Byers

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-β- [(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SKN-MC, and SH- SY5Y). U18666A (≤0.2 μg/ml)completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorboi esterdifferentiated SH-SYSY cells, while reiease stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalNeurochemical Research
Volume24
Issue number1
DOIs
StatePublished - Feb 13 1999
Externally publishedYes

Fingerprint

Neuroblastoma
Neurotransmitter Agents
Cholesterol
Esterification
Norepinephrine
LDL Lipoproteins
Filipin
Sphingomyelin Phosphodiesterase
Calcium Ionophores
LDL Receptors
Calcimycin
LDL Cholesterol
Metabolism
Down-Regulation
3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
Staining and Labeling
Cell Line
Cells
Electric potential

Keywords

  • Cholesterol
  • Neuroblastoma
  • Niemann-Pick C disease
  • Norepinephrine
  • SH-SY5Y
  • U18666A

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells. / Sparrow, Susan M.; Carter, Jodi; Ridgway, Neale D.; Cook, Harold W.; Byers, David M.

In: Neurochemical Research, Vol. 24, No. 1, 13.02.1999, p. 69-77.

Research output: Contribution to journalArticle

Sparrow, Susan M. ; Carter, Jodi ; Ridgway, Neale D. ; Cook, Harold W. ; Byers, David M. / U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells. In: Neurochemical Research. 1999 ; Vol. 24, No. 1. pp. 69-77.
@article{e51362c0c7f3463ca51f9453a8a93fcb,
title = "U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells",
abstract = "To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-β- [(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SKN-MC, and SH- SY5Y). U18666A (≤0.2 μg/ml)completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70{\%} inhibition of K+-evoked norepinephrine release in phorboi esterdifferentiated SH-SYSY cells, while reiease stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired.",
keywords = "Cholesterol, Neuroblastoma, Niemann-Pick C disease, Norepinephrine, SH-SY5Y, U18666A",
author = "Sparrow, {Susan M.} and Jodi Carter and Ridgway, {Neale D.} and Cook, {Harold W.} and Byers, {David M.}",
year = "1999",
month = "2",
day = "13",
doi = "10.1023/A:1020932130753",
language = "English (US)",
volume = "24",
pages = "69--77",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells

AU - Sparrow, Susan M.

AU - Carter, Jodi

AU - Ridgway, Neale D.

AU - Cook, Harold W.

AU - Byers, David M.

PY - 1999/2/13

Y1 - 1999/2/13

N2 - To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-β- [(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SKN-MC, and SH- SY5Y). U18666A (≤0.2 μg/ml)completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorboi esterdifferentiated SH-SYSY cells, while reiease stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired.

AB - To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-β- [(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SKN-MC, and SH- SY5Y). U18666A (≤0.2 μg/ml)completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorboi esterdifferentiated SH-SYSY cells, while reiease stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired.

KW - Cholesterol

KW - Neuroblastoma

KW - Niemann-Pick C disease

KW - Norepinephrine

KW - SH-SY5Y

KW - U18666A

UR - http://www.scopus.com/inward/record.url?scp=0032935277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032935277&partnerID=8YFLogxK

U2 - 10.1023/A:1020932130753

DO - 10.1023/A:1020932130753

M3 - Article

VL - 24

SP - 69

EP - 77

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 1

ER -