scholarly journals Ninjin'yoeito, a traditional Japanese medicine, increases dopamine content in PC12 cells

2021 ◽  
Author(s):  
Shinji Miyazaki ◽  
Yuji Omiya ◽  
Kazushige Mizoguchi
Keyword(s):  
Pc12 Cells ◽  
Metabolic Pathway ◽  
Culture Media ◽  
Metabolic Enzyme ◽  
Metabolizing Enzymes ◽  
Dopamine Content ◽  
Traditional Japanese Medicine ◽  
Dopamine Signaling ◽  
Loss Of Appetite ◽  
Metabolite Content

Abstract Dementia is exacerbated by loss of appetite and amotivation, recent studies have indicated that ninjin'yoeito improves anorexia and amotivation. Previous studies suggest that ninjin'yoeito inhibits dopamine-metabolizing enzymes and enhances dopamine signaling. However, whether ninjin'yoeito increases dopamine content in living cells remains unclear. Here, PC12 cells were used to examine whether ninjin'yoeito affects the dopamine metabolic pathway. Dopamine content significantly increased 3 h after treatment ninjin'yoeito extract. Concomitantly, the levels of 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid was significantly reduced. The effects of components of ninjin'yoeito on the dopamine metabolic pathway were also assessed. Treatment with onjisaponin B, nobiletin, and schisandrin, the ingredients of Polygalae Radix, Citri Unshiu Pericarpium, and Schisandrae Fructus increased dopamine content and decreased its metabolite content in the culture media. Our findings suggest that ninjin'yoeito improves anorexia and amotivation by inhibiting metabolic enzyme and increasing the dopamine content in cells.

Dopaminergic loss of cyclin-dependent kinase-like 5 recapitulates methylphenidate-remediable hyperlocomotion in mouse model of CDKL5 deficiency disorder

2020 ◽  
Vol 29 (14) ◽  
pp. 2408-2419
Author(s):  
Cian-Ling Jhang ◽  
Hom-Yi Lee ◽  
Jin-Chung Chen ◽  
Wenlin Liao
Keyword(s):  
Movement Control ◽  
Motor Dysfunction ◽  
Signaling Proteins ◽  
Cyclin Dependent Kinase ◽  
Serine Threonine Kinase ◽  
Hyperactivity Disorder ◽  
Dopamine Content ◽  
Therapeutic Development ◽  
Dopamine Signaling ◽  
Core Symptoms

Abstract Cyclin-dependent kinase-like 5 (CDKL5), a serine-threonine kinase encoded by an X-linked gene, is highly expressed in the mammalian forebrain. Mutations in this gene cause CDKL5 deficiency disorder, a neurodevelopmental encephalopathy characterized by early-onset seizures, motor dysfunction, and intellectual disability. We previously found that mice lacking CDKL5 exhibit hyperlocomotion and increased impulsivity, resembling the core symptoms in attention-deficit hyperactivity disorder (ADHD). Here, we report the potential neural mechanisms and treatment for hyperlocomotion induced by CDKL5 deficiency. Our results showed that loss of CDKL5 decreases the proportion of phosphorylated dopamine transporter (DAT) in the rostral striatum, leading to increased levels of extracellular dopamine and hyperlocomotion. Administration of methylphenidate (MPH), a DAT inhibitor clinically effective to improve symptoms in ADHD, significantly alleviated the hyperlocomotion phenotype in Cdkl5 null mice. In addition, the improved behavioral effects of MPH were accompanied by a region-specific restoration of phosphorylated dopamine- and cAMP-regulated phosphoprotein Mr 32 kDa, a key signaling protein for striatal motor output. Finally, mice carrying a Cdkl5 deletion selectively in DAT-expressing dopaminergic neurons, but not dopamine receptive neurons, recapitulated the hyperlocomotion phenotype found in Cdkl5 null mice. Our findings suggest that CDKL5 is essential to control locomotor behavior by regulating region-specific dopamine content and phosphorylation of dopamine signaling proteins in the striatum. The direct, as well as indirect, target proteins regulated by CDKL5 may play a key role in movement control and the therapeutic development for hyperactivity disorders.

scholarly journals In silicoidentification of metabolic enzyme drug targets inBurkholderia pseudomallei

2015 ◽  
Author(s):  
Jean F. Challacombe
Keyword(s):  
In Silico ◽  
Drug Targets ◽  
Culture Media ◽  
Metabolic Modeling ◽  
Host Cells ◽  
Natural Resistance ◽  
Metabolic Enzyme ◽  
Chronic Infections ◽  
Genome Scale ◽  
Nutrient Conditions

AbstractThe intracellular pathogenBurkholderia pseudomallei,which is endemic to parts of southeast Asia and northern Australia, causes the disease melioidosis. Although acute infections can be treated with antibiotics, melioidosis is difficult to cure, and some patients develop chronic infections or a recrudescence of the disease months or years after treatment of the initial infection.B. pseudomalleistrains have a high level of natural resistance to a variety of antibiotics, and with limited options for new antibiotics on the horizon, new alternatives are needed. The aim of the present study was to characterize the metabolic capabilities ofB. pseudomallei, identify metabolites crucial for pathogen survival, understand the metabolic interactions that occur between pathogen and host cells, and determine if metabolic enzymes produced by the pathogen might be potential antibacterial targets. This aim was accomplished through genome scale metabolic modeling under different external conditions: 1) including all nutrients that could be consumed by the model, and 2) providing only the nutrients available in culture media. Using this approach, candidate chokepoint enzymes were identified, then knocked outin silicounder the different nutrient conditions. The effect of each knockout on the metabolic network was examined. When five of the candidate chokepoints were knocked outin silico, the flux through theB. pseudomalleinetwork was decreased, depending on the nutrient conditions. These results demonstrate the utility of genome-scale metabolic modeling methods for drug target identification inB. pseudomallei.

scholarly journals Higher percentage of horse serum in culture media blocks attachment of PC12 cells

BioTechniques ◽  
2019 ◽  
Vol 67 (6) ◽  
pp. 256-258
Author(s):  
Jennifer L Meth ◽  
Alan R Schoenfeld
Keyword(s):  
Pc12 Cells ◽  
Culture Media ◽  
Horse Serum

scholarly journals Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Li-Ming Chen ◽  
Chun-Hui Bao ◽  
Yu Wu ◽  
Shi-Hua Liang ◽  
Di Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Metabolic Pathway ◽  
Bowel Disease ◽  
The Body ◽  
Metabolic Enzyme ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Bloody Stools ◽  
The Relationship

AbstractInflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.

scholarly journals Amphetamine reduces vesicular dopamine content in dexamethasone-differentiated PC12 cells only following l-DOPA exposure

2009 ◽  
Vol 111 (2) ◽  
pp. 624-633 ◽  
Author(s):  
Laura Hondebrink ◽  
Jan Meulenbelt ◽  
Johan G. Timmerman ◽  
Martin van den Berg ◽  
Remco H. S. Westerink
Keyword(s):  
Pc12 Cells ◽  
Differentiated Pc12 Cells ◽  
Dopamine Content

scholarly journals Inhibitory Effects of Ethaverine, a Homologue of Papaverine, on Dopamine Content in PC12 Cells.

2001 ◽  
Vol 24 (1) ◽  
pp. 103-105 ◽  
Author(s):  
Jung Soo SHIN ◽  
Jae Joon LEE ◽  
Youngsoo KIM ◽  
Chong Kil LEE ◽  
Yeo Pyo YUN ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Inhibitory Effects ◽  
Dopamine Content

scholarly journals The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells

2008 ◽  
Vol 16 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Yoo-Jung Yang ◽  
Sung-Cil Lim ◽  
Myung-Koo Lee
Keyword(s):  
Pc12 Cells ◽  
Dopamine Content

Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism

2020 ◽  
Vol 27 (10) ◽  
pp. 1038-1045
Author(s):  
Mohd Sami Ur Rasheed ◽  
Manish Kumar Tripathi ◽  
Devendra Kumar Patel ◽  
Mahendra Pratap Singh
Keyword(s):  
Nuclear Translocation ◽  
Neuroblastoma Cells ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Metabolizing Enzymes ◽  
Cyp2d6 Activity ◽  
Xenobiotic Metabolizing Enzymes ◽  
Dopamine Content ◽  
Nrf2 Activation ◽  
Induced Changes

Background: Combined maneb (MB) and paraquat (PQ), two widely used pesticides, increases oxidative stress leading to Parkinsonism. Xenobiotic metabolizing enzymes, cytochrome P450 (CYP) 2D6 and its mouse ortholog Cyp2d22 protect against Parkinsonism. Resveratrol, an antioxidant, restores antioxidant defense system through the activation of nuclear factor erythroid 2- related factor 2 (Nrf2). However, a crosstalk between Cyp2d22/CYP2D6-mediated protection and resveratrol-induced Nrf2 activation leading to neuroprotection is not yet elucidated. Objective: The study aimed to decipher the effect of resveratrol on Nrf2 activation and expression of its downstream mediators, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) and thioredoxin 1 (Trx1) along with Cyp2d22/CYP2D6 activity in combined MB and PQ mouse model of Parkinsonism and differentiated neuroblastoma cells. Results: MB and PQ reduced the dopamine content (mouse) and Cyp2d22/CYP2D6 activity (mouse/neuroblastoma cells) and increased the nuclear translocation of Nrf2 and expression of NQO1 and Trx1 (both). Resveratrol ameliorated pesticides-induced changes in dopamine content and Cyp2d22/CYP2D6 activity. It was found to promote nuclear translocation of Nrf2 and expression of NQO1 and Trx1 proteins. Since Cyp2d22/CYP2D6 inhibitor (ketoconazole/quinidine) per se reduced Cyp2d22/CYP2D6 activity and dopamine content, it was found to substantially increase the pesticides-induced reduction in Cyp2d22/CYP2D6 activity and dopamine content. Inhibitors normalized the pesticides induced changes in Nrf2 translocation and NQO1 and Trx1 levels in pesticides treated groups. Conclusion: The results suggest that resveratrol promotes the catalytic activity of xenobiotic metabolizing enzyme, Cyp2d22/CYP2D6, which partially contributes to Nrf2 activation in pesticides- induced Parkinsonism.

Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3205-3209 ◽  
Author(s):  
Keitaro Matsuo ◽  
Ritsuro Suzuki ◽  
Nobuyuki Hamajima ◽  
Michinori Ogura ◽  
Yoshitoyo Kagami ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Malignant Lymphoma ◽  
Odds Ratio ◽  
Methylenetetrahydrofolate Reductase ◽  
Cancer Center ◽  
Metabolic Enzyme ◽  
Methionine Metabolism ◽  
Metabolizing Enzymes ◽  
Strand Breakage ◽  
Control Study

Abstract Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C→T and MTHFR1298 A→C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A→G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG types. The significance was not altered when these 3 polymorphisms were evaluated in combination, and the results suggest that folate and methionine metabolism play important roles in the occurrence of malignant lymphomas. Further studies to confirm the association and detailed biologic mechanisms are now required.

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