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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Lee SH,Choi NY,Yu HJ,Park J,Choi H,Lee KY,Huh YM,Lee YJ,Koh SH

doi

10.1007/s12035-014-9030-0

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

695-705

issue

1

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-014-9030-0

journal_volume

53

pub_type

杂志文章
  • Presynaptic Regulation of Tonic Inhibition by Neuromodulatory Transmitters in the Basal Amygdala.

    abstract::Tonic inhibition mediated by ambient levels of GABA that activate extrasynaptic GABAA receptors emerges as an essential factor that tunes neuronal network excitability in vitro and shapes behavioral responses in vivo. To address the role of neuromodulatory transmitter systems on this type of inhibition, we employed pa...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-0984-1

    authors: Meis S,Endres T,Munsch T,Lessmann V

    更新日期:2018-11-01 00:00:00

  • HspB1 (Hsp 27) expression and neuroprotection in the retina.

    abstract::Heat shock proteins (Hsps) are highly conserved proteins that are induced in response to various physiological and environmental stressors. HspB1 (Hsp27) is a prominent member of the small Hsps family and is strongly induced during the stress response. Notably, HspB1 has powerful neuroprotective effects, increasing th...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-010-8143-3

    authors: O'Reilly AM,Currie RW,Clarke DB

    更新日期:2010-10-01 00:00:00

  • The Neuroprotection of Lysosomotropic Agents in Experimental Subarachnoid Hemorrhage Probably Involving the Apoptosis Pathway Triggering by Cathepsins via Chelating Intralysosomal Iron.

    abstract::α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid (LA), could protect cells against oxidant challenges via chelating intralysosomal iron. However, the application of LAP in experimental subarachnoid hemorrhage (SAH) is still not well known. This study was designed to evaluate the potential neuroprotection...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8846-y

    authors: Wang Y,Gao A,Xu X,Dang B,You W,Li H,Yu Z,Chen G

    更新日期:2015-08-01 00:00:00

  • Thyroid Hormone Signaling in Oligodendrocytes: from Extracellular Transport to Intracellular Signal.

    abstract::Thyroid hormone plays an important role in central nervous system (CNS) development, including the myelination of variable axonal calibers. It is well-established that thyroid hormone is required for the terminal differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes by inducing ra...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-016-0013-1

    authors: Lee JY,Petratos S

    更新日期:2016-11-01 00:00:00

  • Lysophosphatidylcholine Drives Neuroblast Cell Fate.

    abstract::Neuronal differentiation plays a key role during embryogenesis. However, based on the capacity of neuronal stem cells to either generate or regenerate neurons and because differentiation stops aberrant neuroblasts proliferation, neuronal differentiation is crucial during neuropathological conditions. Although phosphat...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9528-0

    authors: Paoletti L,Domizi P,Marcucci H,Montaner A,Krapf D,Salvador G,Banchio C

    更新日期:2016-11-01 00:00:00

  • Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain.

    abstract::Neurogenesis is a developmental process that involves fine-tuned coordination between self-renewal, proliferation, and differentiation of neural stem cells (NSCs) into neurons. However, early-life assault with environmental toxicants interferes with the regular function of genes, proteins, and other molecules that bui...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02108-9

    authors: Yadav A,Tandon A,Seth B,Goyal S,Singh SJ,Tiwari SK,Agarwal S,Nair S,Chaturvedi RK

    更新日期:2021-01-01 00:00:00

  • Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells.

    abstract::Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0057-2

    authors: Yang H,Liu C,Chen B,An J,Zhang R,Zhang Q,Zhao J,He B,Hao DJ

    更新日期:2017-01-01 00:00:00

  • Cannabinoids and gliomas.

    abstract::Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances--the endocannabinoids--that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-007-0002-5

    authors: Velasco G,Carracedo A,Blázquez C,Lorente M,Aguado T,Haro A,Sánchez C,Galve-Roperh I,Guzmán M

    更新日期:2007-08-01 00:00:00

  • Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

    abstract::There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aβ) and Tau) and exacerbates AD pathology. Neuroinflammation can also ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0795-9

    authors: Magalhães TNC,Weiler M,Teixeira CVL,Hayata T,Moraes AS,Boldrini VO,Dos Santos LM,de Campos BM,de Rezende TJR,Joaquim HPG,Talib LL,Forlenza OV,Cendes F,Balthazar MLF

    更新日期:2018-07-01 00:00:00

  • Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration.

    abstract::Rhodopsin is a G protein-coupled receptor essential for vision and rod photoreceptor viability. Disease-associated rhodopsin mutations, such as P23H rhodopsin, cause rhodopsin protein misfolding and trigger endoplasmic reticulum (ER) stress, activating the unfolded protein response (UPR). The pathophysiologic effects ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8881-8

    authors: Chiang WC,Kroeger H,Sakami S,Messah C,Yasumura D,Matthes MT,Coppinger JA,Palczewski K,LaVail MM,Lin JH

    更新日期:2015-08-01 00:00:00

  • Pre-hospital Delay after Acute Ischemic Stroke in Central Urban China: Prevalence and Risk Factors.

    abstract::Timely thrombolytic treatment is paramount after acute ischemic stroke (AIS); however, a large proportion of patients experience substantial delays in presentation to hospital. This study evaluates the prevalence and risk factors in pre-hospital delays after AIS in central urban China. AIS patients from 66 hospitals i...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9750-4

    authors: Zhou Y,Yang T,Gong Y,Li W,Chen Y,Li J,Wang M,Yin X,Hu B,Lu Z

    更新日期:2017-05-01 00:00:00

  • Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1.

    abstract::Bisphenol A (BPA) is a ubiquitous compound emerging as a possible toxicant during embryonic development. Human embryonic stem cell (hESC) promises a valuable model for evaluating the effects of environmental chemicals on human prenatal development. In our study, 1 μM BPA were applied to hESC-derived embryoid bodies (h...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9898-y

    authors: Huang B,Ning S,Zhang Q,Chen A,Jiang C,Cui Y,Hu J,Li H,Fan G,Qin L,Liu J

    更新日期:2017-07-01 00:00:00

  • 1,25-dyhydroxyvitamin D3 attenuates L-DOPA-induced neurotoxicity in neural stem cells.

    abstract::The neurotoxicity of levodopa (L-DOPA) on neural stem cells (NSCs) and treatment strategies to protect NSCs from this neurotoxicity remain to be elucidated. Recently, an active form of vitamin D3 has been reported to display neuroprotective properties. Therefore, we investigated the protective effect of 1,25-dyhydroxy...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8835-1

    authors: Jang W,Park HH,Lee KY,Lee YJ,Kim HT,Koh SH

    更新日期:2015-04-01 00:00:00

  • Neurotrophins as mediators of drug effects on mood, addiction, and neuroprotection.

    abstract::The induction of synthesis or release of endogenous neurotrophic factors in the brain by low-molecular-weight drugs could be a feasible alternative for the direct administration of neurotrophic factors for the treatment of central nervous system disorders. Recent data suggest that several drugs already in clinical use...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:29:3:289

    authors: Castrén E

    更新日期:2004-06-01 00:00:00

  • α-Synuclein Misfolding Versus Aggregation Relevance to Parkinson's Disease: Critical Assessment and Modeling.

    abstract::α-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in Parkinson's disease (PD). The aggregation of α-synuclein is believed to be a critical event in the disease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different conforma...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8818-2

    authors: Berrocal R,Vasquez V,Rao Krs S,Gadad BS,Rao KS

    更新日期:2015-01-01 00:00:00

  • Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway.

    abstract::Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02095-x

    authors: Zhang XS,Lu Y,Tao T,Wang H,Liu GJ,Liu XZ,Liu C,Xia DY,Hang CH,Li W

    更新日期:2020-12-01 00:00:00

  • The Epilepsy-Related Protein PCDH19 Regulates Tonic Inhibition, GABAAR Kinetics, and the Intrinsic Excitability of Hippocampal Neurons.

    abstract::PCDH19 encodes for protocadherin-19 (PCDH19), a cell-adhesion molecule of the cadherin superfamily preferentially expressed in the brain. PCDH19 mutations cause a neurodevelopmental syndrome named epileptic encephalopathy, early infantile, 9 (EIEE9) characterized by seizures associated with cognitive and behavioral de...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02099-7

    authors: Serratto GM,Pizzi E,Murru L,Mazzoleni S,Pelucchi S,Marcello E,Mazzanti M,Passafaro M,Bassani S

    更新日期:2020-12-01 00:00:00

  • Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation.

    abstract::After its discovery in 2000, the notion grew that neuroglobin, a neuronal specific heme protein, is involved in cytoprotection. To date, neuroglobin levels have been positively correlated with a beneficial outcome in a plethora of neurotoxic insults, e.g., ischemic and traumatic brain injuries and Alzheimer's disease....

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-018-1212-8

    authors: Van Acker ZP,Luyckx E,Dewilde S

    更新日期:2019-03-01 00:00:00

  • Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish.

    abstract::Hypoxia, the major cause of ischemic injury, leads to debilitating disease in infants via birth asphyxia and cerebral palsy, whereas in adults via heart attack and stroke. A widespread, natural protective phenomenon termed 'hypoxic preconditioning' (PH) occurs when prior exposures to hypoxia eventually result in robus...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02091-1

    authors: Das T,Soren K,Yerasi M,Kamle A,Kumar A,Chakravarty S

    更新日期:2020-12-01 00:00:00

  • Dietary Vitamin E Status Dictates Oxidative Stress Outcomes by Modulating Effects of Fish Oil Supplementation in Alzheimer Disease Model APPswe/PS1dE9 Mice.

    abstract::Quite a number of studies have examined the effects of fish oil supplementation on cognitive performance in different transgenic animal models of Alzheimer's disease (AD). However, inconsistent and controversial outcomes have been derived from these experiments. In order to investigate whether the beneficial effect of...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1060-6

    authors: Dong S,Huang X,Zhen J,Van Halm-Lutterodt N,Wang J,Zhou C,Yuan L

    更新日期:2018-12-01 00:00:00

  • HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration.

    abstract::HIV infection and drugs of abuse induce oxidative stress and redox imbalance, which cause neurodegeneration. The mechanisms by which HIV infection and cocaine consumption affect astrocyte energy metabolism, and how this leads to neurodegenerative dysfunction, remain poorly understood. Presently, we investigated how ox...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02131-w

    authors: Sivalingam K,Cirino TJ,McLaughlin JP,Samikkannu T

    更新日期:2021-02-01 00:00:00

  • Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats.

    abstract::Impaired glucose metabolism and mitochondrial decay greatly increase with age, when cognitive decline becomes rampant. No pharmacological or dietary intervention has proven effective, but proper diet and lifestyle do postpone the onset of neurodegeneration and some nutrients are being investigated. We studied insulin ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-0934-y

    authors: Tomé-Carneiro J,Carmen Crespo M,Burgos-Ramos E,Tomas-Zapico C,García-Serrano A,Castro-Gómez P,Venero C,Pereda-Pérez I,Baliyan S,Valencia A,Fontecha J,Dávalos A,Visioli F

    更新日期:2018-09-01 00:00:00

  • Characteristic CSF prion seeding efficiency in humans with prion diseases.

    abstract::The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quak...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8709-6

    authors: Cramm M,Schmitz M,Karch A,Zafar S,Varges D,Mitrova E,Schroeder B,Raeber A,Kuhn F,Zerr I

    更新日期:2015-02-01 00:00:00

  • Anti-neuroinflammatory effect of a novel caffeamide derivative, KS370G, in microglial cells.

    abstract::Accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in several neurodegenerative disorders. Therefore, development of methods for microglial inhibition is considered an important strategy in the search for neuroprotect...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-013-8474-y

    authors: Lu DY,Huang BR,Yeh WL,Lin HY,Huang SS,Liu YS,Kuo YH

    更新日期:2013-12-01 00:00:00

  • Plasma Homocysteine Levels Predict the Risk of Acute Cerebral Infarction in Patients with Carotid Artery Lesions.

    abstract::This study examined the association between elevated plasma homocysteine (Hcy) levels and the risk of acute cerebral infarction in patients with carotid artery lesions. A total of 78 patients were divided into two groups, the high Hcy group (n = 38; Hcy levels >15 umol/L) and the low Hcy group (n = 40; Hcy levels ≤15 ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9226-y

    authors: Wu W,Guan Y,Xu K,Fu XJ,Lei XF,Lei LJ,Zhang ZQ,Cheng Y,Li YQ

    更新日期:2016-05-01 00:00:00

  • Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain.

    abstract::Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0639-7

    authors: Liu S,Zhao Z,Guo Y,Shu H,Li C,Tang Y,Xing Y,Tao F

    更新日期:2018-05-01 00:00:00

  • Different Degrees of Iodine Deficiency Inhibit Differentiation of Cerebellar Granular Cells in Rat Offspring, via BMP-Smad1/5/8 Signaling.

    abstract::Iodine deficiency (ID) during development results in dysfunction of the central nervous system (CNS) and affects psychomotor and motor function. It is worth noting that maternal mild and marginal ID tends to be the most common reason of preventable neurodevelopmental impairment, via a mechanism that has not been eluci...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9382-0

    authors: Dong J,Lei X,Wang Y,Wang Y,Song H,Li M,Min H,Yu Y,Xi Q,Teng W,Chen J

    更新日期:2016-09-01 00:00:00

  • Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons.

    abstract::Neurons with a desired neurotransmitter phenotype can be differentiated from induced pluripotent stem cells or from somatic cells only through tedious protocols with relatively low yield. Readily available cortical neurons isolated from embryonic rat brain, which have already undergone a complete neuronal differentiat...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01701-x

    authors: Raina A,Mahajani S,Bähr M,Kügler S

    更新日期:2020-01-01 00:00:00

  • Neural activity and survival in the developing nervous system.

    abstract::Recent evidence suggests that blockade of normal excitation in the immature nervous system may have profound effects on neuronal survival during the period of natural cell death. Cell loss following depression of electrical activity in the central nervous system (CNS) may explain the neuropsychiatric deficits in human...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:22:1-3:041

    authors: Mennerick S,Zorumski CF

    更新日期:2000-08-01 00:00:00

  • Potential Mechanism of Cellular Uptake of the Excitotoxin Quinolinic Acid in Primary Human Neurons.

    abstract::In Alzheimer's disease (AD), excessive amounts of quinolinic acid (QUIN) accumulate within the brain parenchyma and dystrophic neurons. QUIN also regulates glutamate uptake into neurons, which may be due to modulation of Na+-dependent excitatory amino acid transporters (EAATs). To determine the biological relationship...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02046-6

    authors: Braidy N,Alicajic H,Pow D,Smith J,Jugder BE,Brew BJ,Nicolazzo JA,Guillemin GJ

    更新日期:2021-01-01 00:00:00