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

Title
Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging
Author
이규용
Keywords
Statin; Amyotrophic lateral sclerosis; Phosphatidylinositol 3-kinase; Extracellular signal-related kinase
Issue Date
2016-01
Publisher
Springer
Citation
MOLECULAR NEUROBIOLOGY, v. 53, NO 1, Page. 695-705
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 p85 alpha PI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3 beta, 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.
URI
https://link.springer.com/article/10.1007%2Fs12035-014-9030-0http://hdl.handle.net/20.500.11754/31463
ISSN
0893-7648; 1559-1182
DOI
10.1007/s12035-014-9030-0
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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