Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of aldo-keto reductases

Dan Li, Elizabeth Ellis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) and consequent aldehydic lipid peroxidation products have been identified as significant in the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. Understanding and enhancing endogenous cellular protection against oxidants and aldehydes is therefore of interest in developing strategies to combat these diseases. In this study the role of the aldo-keto reductases AKR7A2 and AKR1C3 in protecting human astrocytoma 1321N1 cells against oxidant and aldehyde toxicity was investigated using siRNA gene silencing. Results show that both enzymes are responsible for part of the intrinsic protection against aldehydes and oxidants. Treating cells with sub-lethal concentrations of oxidant or aldehyde stress or with the natural coumarin 7-hydroxycoumarin (umbelliferone) revealed that endogenous resistance to aldehydes and oxidants can be induced significantly. The basis of the inducible protection by 7-hydroxycoumarin was shown to be associated with induction of the aldo-keto reductases AKR7A2 (1.5-fold) and AKR1 C (3-fold), and this inducible protection was sufficient to overcome siRNA silencing of AKR1C3. These results indicate the importance of AKR family members in the detoxication of aldehydes, and also show that the natural phytochemical 7-hydroxycoumarin is a potential therapeutic candidate for neurodegenerative diseases.
LanguageEnglish
Pages1368-1374
Number of pages7
JournalNeuroToxicology
Volume33
Issue number5
Early online date7 Sep 2012
DOIs
Publication statusPublished - Oct 2012

Fingerprint

7-hydroxycoumarin
Astrocytoma
Aldehydes
Hydrogen Peroxide
Toxicity
Oxidants
Up-Regulation
Neurodegenerative diseases
Neurodegenerative Diseases
Small Interfering RNA
Phytochemicals
Gene Silencing
Lipid Peroxidation
carbonyl reductase (NADPH)
Reactive Oxygen Species
Genes

Keywords

  • inducible protection
  • human astrocytoma
  • 1321N1 cells
  • hydrogen peroxide
  • aldehyde toxicity
  • 7-hydroxycoumarin
  • upregulation
  • aldo-keto reductases

Cite this

@article{a0856ba329a44d869af7a39e640c4bfe,
title = "Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of aldo-keto reductases",
abstract = "Reactive oxygen species (ROS) and consequent aldehydic lipid peroxidation products have been identified as significant in the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. Understanding and enhancing endogenous cellular protection against oxidants and aldehydes is therefore of interest in developing strategies to combat these diseases. In this study the role of the aldo-keto reductases AKR7A2 and AKR1C3 in protecting human astrocytoma 1321N1 cells against oxidant and aldehyde toxicity was investigated using siRNA gene silencing. Results show that both enzymes are responsible for part of the intrinsic protection against aldehydes and oxidants. Treating cells with sub-lethal concentrations of oxidant or aldehyde stress or with the natural coumarin 7-hydroxycoumarin (umbelliferone) revealed that endogenous resistance to aldehydes and oxidants can be induced significantly. The basis of the inducible protection by 7-hydroxycoumarin was shown to be associated with induction of the aldo-keto reductases AKR7A2 (1.5-fold) and AKR1 C (3-fold), and this inducible protection was sufficient to overcome siRNA silencing of AKR1C3. These results indicate the importance of AKR family members in the detoxication of aldehydes, and also show that the natural phytochemical 7-hydroxycoumarin is a potential therapeutic candidate for neurodegenerative diseases.",
keywords = "inducible protection , human astrocytoma , 1321N1 cells , hydrogen peroxide , aldehyde toxicity, 7-hydroxycoumarin, upregulation , aldo-keto reductases",
author = "Dan Li and Elizabeth Ellis",
year = "2012",
month = "10",
doi = "10.1016/j.neuro.2012.08.015",
language = "English",
volume = "33",
pages = "1368--1374",
journal = "NeuroToxicology",
issn = "0161-813X",
number = "5",

}

TY - JOUR

T1 - Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of aldo-keto reductases

AU - Li, Dan

AU - Ellis, Elizabeth

PY - 2012/10

Y1 - 2012/10

N2 - Reactive oxygen species (ROS) and consequent aldehydic lipid peroxidation products have been identified as significant in the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. Understanding and enhancing endogenous cellular protection against oxidants and aldehydes is therefore of interest in developing strategies to combat these diseases. In this study the role of the aldo-keto reductases AKR7A2 and AKR1C3 in protecting human astrocytoma 1321N1 cells against oxidant and aldehyde toxicity was investigated using siRNA gene silencing. Results show that both enzymes are responsible for part of the intrinsic protection against aldehydes and oxidants. Treating cells with sub-lethal concentrations of oxidant or aldehyde stress or with the natural coumarin 7-hydroxycoumarin (umbelliferone) revealed that endogenous resistance to aldehydes and oxidants can be induced significantly. The basis of the inducible protection by 7-hydroxycoumarin was shown to be associated with induction of the aldo-keto reductases AKR7A2 (1.5-fold) and AKR1 C (3-fold), and this inducible protection was sufficient to overcome siRNA silencing of AKR1C3. These results indicate the importance of AKR family members in the detoxication of aldehydes, and also show that the natural phytochemical 7-hydroxycoumarin is a potential therapeutic candidate for neurodegenerative diseases.

AB - Reactive oxygen species (ROS) and consequent aldehydic lipid peroxidation products have been identified as significant in the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. Understanding and enhancing endogenous cellular protection against oxidants and aldehydes is therefore of interest in developing strategies to combat these diseases. In this study the role of the aldo-keto reductases AKR7A2 and AKR1C3 in protecting human astrocytoma 1321N1 cells against oxidant and aldehyde toxicity was investigated using siRNA gene silencing. Results show that both enzymes are responsible for part of the intrinsic protection against aldehydes and oxidants. Treating cells with sub-lethal concentrations of oxidant or aldehyde stress or with the natural coumarin 7-hydroxycoumarin (umbelliferone) revealed that endogenous resistance to aldehydes and oxidants can be induced significantly. The basis of the inducible protection by 7-hydroxycoumarin was shown to be associated with induction of the aldo-keto reductases AKR7A2 (1.5-fold) and AKR1 C (3-fold), and this inducible protection was sufficient to overcome siRNA silencing of AKR1C3. These results indicate the importance of AKR family members in the detoxication of aldehydes, and also show that the natural phytochemical 7-hydroxycoumarin is a potential therapeutic candidate for neurodegenerative diseases.

KW - inducible protection

KW - human astrocytoma

KW - 1321N1 cells

KW - hydrogen peroxide

KW - aldehyde toxicity

KW - 7-hydroxycoumarin

KW - upregulation

KW - aldo-keto reductases

U2 - 10.1016/j.neuro.2012.08.015

DO - 10.1016/j.neuro.2012.08.015

M3 - Article

VL - 33

SP - 1368

EP - 1374

JO - NeuroToxicology

T2 - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

IS - 5

ER -