Role of the phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways in the neuroprotective effects of cilnidipine against hypoxia in a primary culture of cortical neurons

Kim, Sangjae; Lee, Kyu-Yong; Koh, Seong‐Ho; Park, Hyun‐Hee; Yu, Hyun-Jeung; Lee, Young Joo

doi:10.1016/j.neuint.2012.08.010

Cited by 7 publications

(9 citation statements)

References 43 publications

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“…10 12.20), which is in agreement with the morphology assay in our previous study (data not shown) [4] (Fig. Therefore, we examined whether the neurotrophic effect of MDHB was because of activation of the MAPK signal (Erk1/2) or the PI3K signal (Akt).…”

Section: Effect Of Inhibitors On Mdhb-induced Neurite Outgrowthsupporting

confidence: 82%

Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway

Zhang

Cai²,

Zhou

et al. 2015

NeuroReport

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Methyl 3,4-dihydroxybenzoate (MDHB), a kind of phenolic acid compounds, has been reported to have antioxidant effects. Moreover, our previous study found that it could promote neurite outgrowth and brain-derived neurotrophic factor expression in cortical neurons of neonatal rats. In the present study, we focused on the mechanism of its neurotrophic effect; the results showed that MDHB-induced upregulation of neuronal survival and neurite outgrowth in cultured primary cortical neurons could be blocked by the adenosine A2a receptor inhibitor (ZM241385) and the phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). Subsequently, we found that the upregulation of Akt phosphorylation by MDHB could be suppressed by A2a-R and PI3K-specific inhibitor, but not the Trk-R inhibitor. Furthermore, MDHB could activate Akt in a concentration-dependent manner. These results suggested that activation of the PI3K/Akt signaling pathway may be involved in the MDHB-induced neurotrophic effects and MDHB could be a candidate compound to develop drugs for neurodegenerative disease.

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Section: Effect Of Inhibitors On Mdhb-induced Neurite Outgrowthsupporting

confidence: 82%

Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway

Zhang

Cai²,

Zhou

et al. 2015

NeuroReport

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“…pAkt can also move to the nucleus and regulate some transcriptional factors [15,16]. The ERK pathway also plays an important role in neuronal cell survival [33,34]. In neurons, ERK is mainly activated by growth factors and is associated with cell proliferation, differentiation, and development [33,34].…”

Section: Discussionmentioning

confidence: 99%

“…The ERK pathway also plays an important role in neuronal cell survival [33,34]. In neurons, ERK is mainly activated by growth factors and is associated with cell proliferation, differentiation, and development [33,34]. Such actions are best examined in the context of growth factor signaling via receptor tyrosine kinases [33,34].…”

Section: Discussionmentioning

confidence: 99%

“…In neurons, ERK is mainly activated by growth factors and is associated with cell proliferation, differentiation, and development [33,34]. Such actions are best examined in the context of growth factor signaling via receptor tyrosine kinases [33,34]. Receptor tyrosine kinases activate downstream targets such as small G proteins, Ras, Raf-1, and mitogen-activated protein kinase kinase (MEK).…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Choi

et al. 2015

Mol Neurobiol

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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.

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“…The TUNEL staining kit (In Situ Cell Death Detection Kit, TMR red, Roche, New York, NY 10016, USA) could detect and quantify apoptosis at the single cell level based on DNA strand break labeling (Kim et al, 2012;Sarkissian et al, 2014). The kit was used according to the manufacturer's instructions.…”

Section: Tunel and Dapi Stainingmentioning

confidence: 99%

Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B

Chi

Meng

et al. 2014

Brain Research

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Role of the phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways in the neuroprotective effects of cilnidipine against hypoxia in a primary culture of cortical neurons

Cited by 7 publications

References 43 publications

Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway

Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor/PI3K/Akt signaling pathway

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

Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B

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