Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

Seok Ho Lee, Na Young Choi, Hyun Jeung Yu, Jinse Park, Hojin Choi, Kyu Yong Lee, yongmin Huh, Young Joo Lee, Seong Ho Koh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.

Original languageEnglish
Pages (from-to)695-705
Number of pages11
JournalMolecular Neurobiology
Volume53
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Phosphatidylinositol 3-Kinase
Motor Neurons
Free Radicals
Oxidative Stress
Phosphotransferases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Neuroprotective Agents
Intracellular Signaling Peptides and Proteins
Glycogen Synthase Kinase 3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Trypan Blue
Caspase 9
Amyotrophic Lateral Sclerosis
Cytochromes
Atorvastatin Calcium
Fluorescent Dyes
Caspase 3
Hydrogen Peroxide
Cell Survival
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Lee, Seok Ho ; Choi, Na Young ; Yu, Hyun Jeung ; Park, Jinse ; Choi, Hojin ; Lee, Kyu Yong ; Huh, yongmin ; Lee, Young Joo ; Koh, Seong Ho. / Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging. In: Molecular Neurobiology. 2016 ; Vol. 53, No. 1. pp. 695-705.
@article{89c15e647c994d9eb76a409613ba610d,
title = "Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging",
abstract = "Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.",
author = "Lee, {Seok Ho} and Choi, {Na Young} and Yu, {Hyun Jeung} and Jinse Park and Hojin Choi and Lee, {Kyu Yong} and yongmin Huh and Lee, {Young Joo} and Koh, {Seong Ho}",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s12035-014-9030-0",
language = "English",
volume = "53",
pages = "695--705",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "1",

}

Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging. / Lee, Seok Ho; Choi, Na Young; Yu, Hyun Jeung; Park, Jinse; Choi, Hojin; Lee, Kyu Yong; Huh, yongmin; Lee, Young Joo; Koh, Seong Ho.

In: Molecular Neurobiology, Vol. 53, No. 1, 01.01.2016, p. 695-705.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

AU - Lee, Seok Ho

AU - Choi, Na Young

AU - Yu, Hyun Jeung

AU - Park, Jinse

AU - Choi, Hojin

AU - Lee, Kyu Yong

AU - Huh, yongmin

AU - Lee, Young Joo

AU - Koh, Seong Ho

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.

AB - Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.

UR - http://www.scopus.com/inward/record.url?scp=84953209304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953209304&partnerID=8YFLogxK

U2 - 10.1007/s12035-014-9030-0

DO - 10.1007/s12035-014-9030-0

M3 - Article

C2 - 25577170

AN - SCOPUS:84953209304

VL - 53

SP - 695

EP - 705

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 1

ER -