Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson’s Disease

Khwanraj, Kawinthra; Madlah, Suriyat; Grataitong, Khwanthana; Dharmasaroja, Permphan

doi:10.1155/2016/8716016

Cited by 28 publications

(35 citation statements)

References 48 publications

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“…PI3K-AKT activation is associated with neuronal activities, including proliferation, apoptosis, differentiation and metabolism (33). PI3K-AKT dysregulation is critical in the development of CNS diseases, including Parkinson's Disease, ischemic brain injury and epilepsy (34)(35)(36). In the present study it was demonstrated that p-AKT expression decreased significantly in astrocytes in an epileptic environment.…”

Section: Discussionsupporting

confidence: 53%

CB2R induces a protective response for epileptic seizure via the PI3K 110α‑AKT signaling pathway

et al. 2018

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Epilepsy is a chronic brain disease caused by abnormal discharging in the brain, which induces momentary brain dysfunction. Cannabinoid 2 receptor (CB2R) is expressed in central nervous system (CNS) and serves an important role in the pathogenesis of CNS diseases. The aim of the present study was to explore the effects of CB2R activation on phosphoinositide 3-kinase (PI3K) 110α-protein kinase B (AKT) signaling in an astrocyte model of epilepsy. Rat CTX TNA2 astrocytes were treated with Mg free solution to establish a cell model of epilepsy and were subsequently treated with a CB2R agonist (JWH133) and antagonist (AM630). Cell cycle analysis revealed that treatment using Mg free solution inhibited cell cycle transition. JWH133 facilitated cell cycle progression while AM630 inhibited it. Western blotting results demonstrated that treatment with Mg free solution downregulated the expression of cyclin D1, cyclin E, phosphorylated Retinoblastoma (p-Rb), B-cell lymphoma 2 (Bcl-2), PI3K 110α, p-AKT and p-mammalian target of rapamycin, whereas JWH133 treatment upregulated these proteins. AM630 ameliorated the JWH133-induced upregulation of these proteins. To confirm the involvement of AKT signaling, the AKT inhibitor wortmannin was used. The results revealed that wortmannin inhibited the effect of JWH133 on p-AKT, cyclin D1, p-Rb and Bcl-2 expression. In addition, the effects of JWH133 and AM630 on PI3K 110α-AKT signaling were verified using a rat model of epilepsy. In conclusion, the present study demonstrates that CB2R activation induces astrocyte proliferation and survival via activation of the PI3K 110α-AKT signaling pathway.

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Section: Discussionsupporting

confidence: 53%

CB2R induces a protective response for epileptic seizure via the PI3K 110α‑AKT signaling pathway

et al. 2018

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“…Dopaminergic degeneration is still a mystery for scientists. Many researchers directed the investigations towards pathogenesis, [46][47][48] epidemiology, pathology, and genetics. While major research signs of progress have been made, as well as the current recognizable proof of conceivable environmental and genetic risk factors for PD, further molecular docking studies are performed to detect the molecular interactions, active site prediction, and drug interaction based studies and cellular pathway research is necessary to explicate the root causes of PD and to discover enhanced treatments.…”

Section: Resultsmentioning

confidence: 99%

“…6,7 Many shreds of evidence suggest that phosphatidylinositol-3 kinase (PI3K)/Akt (protein kinase-B)/mammalian target of the rapamycin (mTOR) pathway (PI3K/Akt/mTOR) pathway signaling related to dopaminergic neuron degeneration in PD. [46][47][48] The neuron degeneration concurrently influences the wider region of the brain responsible for dementia.…”

Section: Introductionmentioning

confidence: 99%

A review on factors causing parkinson’s syndrome

Shanmughavel¹,

Selvaraj²

2018

MOJPB

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Parkinson disease (PD) is the most common chronic neurodegenerative disease that affects the brain, resulting in a progressive loss of coordination and movement to death and contributes to about 25-30% cases of dementia. An estimated seven million to 10million people worldwide have Parkinson's disease. It is characterized by the classical motor features of parkinsonism related to Lewy bodies and loss of dopaminergic neurons in the substantia nigra, and the major symptoms include problems with resting tremor, rigidity, bradykinesia, postural instability, speech dysfunction, psychiatric symptoms, sleep disorder and fatigue. Presently existing pharmacological and surgical treatments provides relief from a few motor symptoms, but do not halt the ultimate progression of the syndrome. The root cause of Parkinson's disease remains unknown. Although significant research advances illustrate distinct paths that closely try to disclose various mitochondrial, genetic, behavioral, environmental, and epigenetic causes that may lead to the development of PD. Most likely all study target the dysfunction of the ubiquitin-proteasome pathway, alpha-synuclein protein, PINK1 protein, PI3K/Akt/mTOR pathway. However, a better understanding of the disease is leading to new diagnostic tools and treatments.

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“…Interestingly, previous studies reported that the eEF1A declined in the human brain tissues with history of PD disease progression, indicating an association of eEF1A and altered polypeptide synthesis in the corresponding area (Licker et al, 2014;Garcia-Esparcia et al, 2015). In the cellular model, upregulation of genes of eEF1A has been found to be associated with the increased expression of PI3K, AKT, and mTOR in 1methyl-4-phenylpyridinium (MPP+)-induced cellular PD model (Khwanraj et al, 2016). Since the roles of eEF1A1 and eEF1A2 in the prevention of DA neuronal cell death in PD remain unclear, this study aims to investigate the role of eEF1A isoforms on degenerated DA neurons by using Caenorhabditis elegans as a PD model.…”

Section: Introductionmentioning

confidence: 95%

“…Having revealed a role for eEF1A in PI3K/AKT/mTOR mechanism in several cellular models (Amiri et al, 2006;Khwanraj et al, 2016), we sought to examine whether the eft-3 and eft-4 mediate neuroprotection through the cell survival signaling, PI3K/AKT/mTOR, in 6-OHDA-induced C. elegans PD model. We performed real-time qPCR to analyze the mRNA levels of daf-2, age-1, let-363, pdk-1, akt-1, and akt-2, which are homologs with cell-survival signaling genes in mammals.…”

Section: Decreasing Of Eft-3 or Eft-4 Affected The Survival Gene Exprmentioning

confidence: 99%

Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model

2020

Self Cite

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein protein and selective death of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Although the molecular pathogenesis of PD is not completely understood, a recent study has reported that eukaryotic translation elongation factor 1 alpha (eEF1A) declined in the PD-affected brain. Therefore, the roles of eEF1A1 and eEF1A2 in the prevention of DA neuronal cell death in PD are aimed to be investigated. Herein, by using Caenorhabditis elegans as a PD model, we investigated the role of eft-3/eft-4, the worm homolog of eEF1A1/eEF1A2, on 6-hydroxydopamine (6-OHDA)-induced DA neuron degeneration. Our results demonstrated that the expressions of eft-3 and eft-4 were decreased in the 6-OHDA-induced worms. RNA interference (RNAi) of eft-3 and eft-4 resulted in dramatic exacerbation of DA neurodegeneration induced by 6-OHDA, as well as aggravated the food-sensing behavior, ethanol avoidance, and decreased lifespan when compared with only 6-OHDA-induced worms. Moreover, downregulation of eft-3/4 in 6-OHDA-induced worms suppressed the expression of the anti-apoptotic genes, including PI3K/age-1, PDK-1/pdk-1, mTOR/let-363, and AKT-1,2/akt-1,2, promoting the expression of apoptotic genes such as BH3/egl-1 and Caspase-9/ced-3. Collectively, these findings indicate that eEF1A plays an important role in the 6-OHDA-induced neurodegeneration through the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)/mammalian target of rapamycin (mTOR) pathway and that eEF1A isoforms may be a novel and effective pro-survival factor in protective DA neurons against toxin-induced neuronal death.

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Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson’s Disease

Cited by 28 publications

References 48 publications

CB2R induces a protective response for epileptic seizure via the PI3K 110α‑AKT signaling pathway

CB2R induces a protective response for epileptic seizure via the PI3K 110α‑AKT signaling pathway

A review on factors causing parkinson’s syndrome

Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model

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