scholarly journals Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells: relevance to the pathogenesis of Parkinson's disease

2012 ◽  
Vol 123 (6) ◽  
pp. 932-943 ◽  
Author(s):  
David S. Goldstein ◽  
Patti Sullivan ◽  
Adele Cooney ◽  
Yunden Jinsmaa ◽  
Rachel Sullivan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Vesicular Uptake

scholarly journals Grafting of Encapsulated Dopamine-Secreting Cells in Parkinson's Disease: Long-Term Primate Study

2000 ◽  
Vol 9 (5) ◽  
pp. 705-709 ◽  
Author(s):  
Isao Date ◽  
Tetsuro Shingo ◽  
Hideyuki Yoshida ◽  
Kenjiro Fujiwara ◽  
Kazuki Kobayashi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Tumor Formation ◽  
Functional Improvement ◽  
Functional Changes ◽  
Polymer Encapsulation ◽  
Encapsulated Cells ◽  
Fluid Analysis

The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.

scholarly journals Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2761 ◽  
Author(s):  
Sandra Buratta ◽  
Elisabetta Chiaradia ◽  
Alessia Tognoloni ◽  
Angela Gambelunghe ◽  
Consuelo Meschini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Cell Function ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Protein Damage ◽  
Substantia Nigra Pars Compacta

Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.

Effects of (-)-sesamin on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and dopaminergic neuronal cells of Parkinson's disease rat models

2015 ◽  
Vol 83-84 ◽  
pp. 19-27 ◽  
Author(s):  
Hyun Jin Park ◽  
Ting Ting Zhao ◽  
Kyung Sook Lee ◽  
Seung Ho Lee ◽  
Keon Sung Shin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Neuronal Cells ◽  
Rat Models ◽  
6 Hydroxydopamine

scholarly journals Interactive Responses of Enkephalin, δ-opioid Receptor and Dopamine Receptor D1/D2 to Hypoxia and/or MPP+ Stress in PC12 Cells

2021 ◽  
Author(s):  
Tao Chen ◽  
Qing-Yu Wang ◽  
Dong-Man Chao ◽  
Yi-Dong Deng ◽  
Yan-Hui Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Receptor ◽  
Pc12 Cells ◽  
Opioid Receptor ◽  
Mrna Level ◽  
Cell Protection ◽  
Endogenous Opioid ◽  
Δ Opioid Receptor

Abstract Hypoxic/ischemic brain injury is a potential etiology of Parkinson’s disease (PD). There is evidence suggesting that the up-regulation of enkephalin, an endogenous opioid, in the midbrain may have a compensatory effect against Parkinson’s disease (PD) related motor symptoms. To explore the potential mechanism underlying this action, we investigated the effects of hypoxia and MPP+, a pathological inducer PD, on enkephalin, δ-opioid receptor (DOR, an enkephalin receptor), and prohormone convertases 1 and 2 (PC1/PC2) on in- vitro PD model of PC12 cells. We found that (1) short-term hypoxia could inducing cell protection by up-regulating the level of enkephalin, accompanied by the synergistic up-regulation of δ-opioid receptor (DOR) ; (2) a longer period of hypoxia or MPP+ insult accelerated the proteolysis of proenkephalin by up-regulating PC1/PC2 which might produce more active enkephalin and thus activating DOR for cell protection; (3) The levels of enkephalin and DOR decreased significantly after a prolonged hypoxia or MPP+ insult; and (4) a certain degree of hypoxia improved cell viability and enhance the transcription of dopamine D1/D2 receptorby increasing their mRNA level. Our findings suggest that hypoxia may induce an interactive reaction of enkephalin, DOR and dopamine receptor D1/D2, which is potentially beneficial for cell surviving to severe/prolonged hypoxia and PD condition.

scholarly journals Influence of N6-Methyladenosine Modification Gene HNRNPC on Cell Phenotype in Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Wei Quan ◽  
Jia Li ◽  
Li Liu ◽  
Qinghui Zhang ◽  
Yidan Qin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Inflammatory Factors ◽  
Cell Phenotype ◽  
Data Sets ◽  
And Function ◽  
Experimental Group

This study aimed to explore the N6-methyladenosine (m6A) modification genes involved in the pathogenesis of Parkinson’s disease (PD) through data analysis of the two data sets GSE120306 and GSE22491 in the GEO database and further explore its influence on cell phenotype in PD. We analyzed the differentially expressed genes and function enrichment analysis of the two sets of data and found that the expression of the m6A-modification gene HNRNPC was significantly downregulated in the PD group, and it played an important role in DNA metabolism, RNA metabolism, and RNA processing and may be involved in PD. Then, we constructed the HNRNPC differential expression cell line to study the role of this gene in the pathogenesis of PD. The results showed that overexpression of HNRNPC can promote the proliferation of PC12 cells, inhibit their apoptosis, and inhibit the expression of inflammatory factors IFN-β, IL-6, and TNF-α, suggesting that HNRNPC may cause PD by inhibiting the proliferation of dopaminergic nerve cells, promoting their apoptosis, and causing immune inflammation. Our study also has certain limitations. For example, the data of the experimental group and the validation group come from different cell types, and the data of the experimental group involve individuals with G2019S LRRK2 mutations. In addition, due to the low expression of HNRNPC in PC12 cells, we used the method of overexpressing this gene to study its function. All these factors may cause our conclusions to be biased. Therefore, more research is still needed to corroborate it in the future.

scholarly journals Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

2021 ◽  
Author(s):  
Xiao Yan Sheng ◽  
Shui Yuan Yang ◽  
Xiao Min Wen ◽  
Xin Zhang ◽  
Yong Feng Ye ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Motor Behavior ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Dopamine Neurons ◽  
Therapeutic Modality ◽  
Neuroprotective Effects

Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

Pre-treatment with R-Lipoic Acid Alleviates the Effects of GSH Depletion in PC12 Cells: Implications for Parkinson’s Disease Therapy

2002 ◽  
Vol 23 (4-5) ◽  
pp. 479-486 ◽  
Author(s):  
S. Bharath ◽  
B.C. Cochran ◽  
M. Hsu ◽  
J. Liu ◽  
B.N. Ames ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Lipoic Acid ◽  
Disease Therapy ◽  
Pre Treatment

scholarly journals Neuroprotective Effects of Cuscutae Semen in a Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Minsook Ye ◽  
Seul gi Lee ◽  
Eun Sook Chung ◽  
Su-jin Lim ◽  
Won Seob Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Glutathione Peroxidase ◽  
Pc12 Cells ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Ros Generation ◽  
Neuroprotective Effects ◽  
Differentiated Pc12 Cells

Parkinson’s disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain’s immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD.

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