• The Korean Journal of Physiology and Pharmacology
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• 제15권4호
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• pp.245-249
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• 2011

Amphetamine, a synthetic psychostimulant, is transported by the dopamine transporter (DAT) to the cytosol and increases the exchange of extracellular amphetamine by intracellular dopamine. Recently, we reported that the phosphorylation levels of ezrin-radixin-moesin (ERM) proteins are regulated by psychostimulant drugs in the nucleus accumbens, a brain area important for drug addiction. However, the significance of ERM proteins phosphorylation in response to drugs of abuse has not been fully investigated. In this study, using PC12 cells as an in vitro cell model, we showed that amphetamine increases ERM proteins phosphorylation and protein kinase C (PKC) ${\beta}$ inhibitor, but not extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinases (PI3K) inhibitors, abolished this effect. Further, we observed that DAT inhibitor suppressed amphetamine-induced ERM proteins phosphorylation in PC12 cells. These results suggest that $PKC{\beta}$-induced DAT regulation may be involved in amphetmaine-induced ERM proteins phosphorylation.

• Natural Product Sciences
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• 제24권2호
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• pp.99-102
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• 2018

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and $10{\mu}M$ increased intracellular dopamine levels at 1 - 24 h. Ombuoside (1, 5, and $10{\mu}M$) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 - 6 h. In addition, ombuoside (1, 5, and $10{\mu}M$) combined with L-DOPA (20, 100, and $200{\mu}M$) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.

• BMB Reports
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• 제41권2호
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• pp.146-152
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• 2008

In the presence of NGF, PC12 cells extend neuronal processes, cease cell division, become electrically excitable, and undergo several biochemical changes that are detectable in developing sympathetic neurons. We investigated the expression pattern of the apoptosis-related genes at each stage of neuronal differentiation using a cDNA microarray containing 320 apoptosis-related rat genes. By comparing the expression patterns through time-series analysis, we identified candidate genes that appear to regulate neuronal differentiation. Among the candidate genes, HO2 was selected by real-time PCR and Western blot analysis. To identify the roles of selected genes in the stages of neuronal differentiation, transfection of HO2 siRNA in PC12 cells was performed. Down-regulation of HO2 expression causes a reduction in neuronal differentiation in PC12 cells. Our results suggest that the HO2 gene could be related to the regulation of neuronal differentiation levels.

• Toxicological Research
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• 제29권4호
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• pp.235-240
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• 2013

Extracellular accumulation of amyloid beta protein ($A{\beta}$) plays a central role in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can affect the $A{\beta}$ accumulation in the brain. However, the effect of mercury on $A{\beta}$ accumulation in the brain is not clear. Thus, this study was proposed to estimate whether mercury concentration affects $A{\beta}$ accumulation in PC12 cells. We treated 10, 100, and 1000 nM $HgCl_2$ (Hg) or $CH_3HgCl_2$ (MeHg) for 48 hr in PC12 cells. After treatment, $A{\beta}_{40}$ in culture medium increased in a dose- and time-dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is related to $A{\beta}$ production. Neprilysin (NEP) levels in PC12 cells were decreased by Hg and MeHg treatment. These results suggested that Hg induced $A{\beta}$ accumulation through APP overproduction and reduction of NEP.

• Mycobiology
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• 제35권1호
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• pp.11-15
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• 2007

We examined the neuroprotective and neurotrophic effects of Tremella fuciformis. The neurotrophic effects of the hot water extract of T. fuciformis was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The hot water extract cf T. fuciformis promoted neurite outgrowth in PC12h cells in this study, superior to other natural substances which was reported previously. When cells were treated with the hot water extract of T. fuciformis prior to ${\beta}$-amyloid peptide treatment (active domain of A peptide $35{\sim}35$ treated), toxicity was significantly diminished (p<0.01). These results suggest that T. fuciformis might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.

• 한국식품과학회지
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• 제37권3호
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• pp.479-483
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• 2005

느릅나무 에탄올 추출물의 각 용매 분획물에 대한 항산화활성과 L-glutamate에 의하여 유도된 PC 12세포에 대한 세포 독성 및 세포 내 활성산소종(ROS)을 측정하였다. 느릅나무 수피의 에틸아세테이트 및 부탄올 분획과 근피의 에틸아세테이트 분획층은 흰쥐 뇌조직에서 $FeSO_{4}-H_{2}O_{2}$로 유도한 산화적 스트레스를 유의하게 억제하였으며 강한 fire radical 소거능을 나타내었다. 또한 glutamate에 의하여 PC 12 세포의 생존율이 억제되었고 세포내 ROS가 증가하였으며 이러한 ROS의 증가는 근피의 에틸아세테이트 및 부탄올 획분에 의하여 억제되었다. 따라서 느릅나무 근피의 에틸아세테이트 및 부탄올 획분은 PC 12 세포에서 glutamate로 유도된 세포내 ROS를 억제함으로써 세포의 독성을 보호한 것으로 사료되었다.

• Natural Product Sciences
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• 제10권3호
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• pp.119-123
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• 2004

The effects of BHSH on L-DOPA-induced increase in dopamine content in PC12 cells were investigated. L-DOPA treatment at $20\;or\;50\;{\mu}M$ increased dopamine content after both 24 and 48 h of incubation in PC12 cells. However, the co-treatments of BHSH $(10-50\;{\mu}M)$ with L-DOPA $(20\;or\;50\;{\mu}M)$ significantly inhibited the increase of dopamine content induced by L-DOPA. BHSH treatment at $10-50\;{\mu}M$ significantly inhibited basal aromatic L-amino acid decarboxylase (AADC) activity in a concentration-dependent manner at 15 min, and then AADC activity was rapidly recovered to the control level at about 2 h. These results indicate that the inhibition of AADC activity by BHSH was, in part, contributed to the early-stage decrease of dopamine content induced by LDOPA in PC12 cells. Taken together, it is proposed that the short-term inhibition of dopamine biosynthesis by BHSH was mediated by the regulation of tyrosine hydroxylace (TH).

• 생약학회지
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• 제40권4호
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• pp.351-356
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• 2009

Many isoquinoline alkaloids including berberine lower dopamine content by reducing tyrosine hydroxylase (TH) activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rat models were investigated. Berberine at 10-30 ${\mu}M$ did not affect cell viability in PC12 cells. However, berberine at concentrations higher than $50{\mu}M$ caused cytotoxicity at 24 h. Berberine (10-50 ${\mu}M$) also enhanced 6-OHDA (10-50 ${\mu}M$)-induced cytotoxicity at 24 h compared to 6-OHDA alone with an apoptotic process. In addition, treatment with berberine (5 and 30 mg/kg, i.p.) for three weeks showed a dopaminergic cell loss in substantia nigra of 6-OHDA-lesioned rats: 30 mg/kg berberine was more intensive cytotoxic. The levels of dopamine were also decreased by berberine (5 and 30 mg/kg) in the ipsilateral substantia nigra of 6-OHDA-lesioned rats. These results suggest that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells and treatment with berberine (5 and 30 mg/kg) in 6-OHDA-lesioned rats also enhanced the degeneration of dopaminergic cell death and the decrease in dopamine levels in substantia nigra. Therefore, the long-term L-DOPA therapeutic patients with isoquinoline compounds including berberine may need to be checked for the adverse symptoms.

• 동의신경정신과학회지
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• 제20권1호
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• pp.21-42
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• 2009

Objectives : This Study was performed to assess the antioxidant and neuroprotective effect of Chunghyul-dan(Qingxuedan) in PC12 cells and primary rat mesencephalic dopaminergic neurons. Methods : The anioxidant effect was investigated using the DPPH radical and ABTS cation scavenging assays and total polyphenol amout of Chunghyul-dan(Qingxuedan). The neuroprotective effect of Chunghyul-dan(Qingxuedan) in PC12 cells was evaluated using MTT assay. The scavenging activity of Chunghyul-dan(Qingxuedan) on ROS production induced by 6-OHDA(6-hydroxydopamine) in PC12 cells was evaluated, as well as the attenuating effect on GSH reduction. Finally, we examined the neuroprotective effect of Chunghyul-dan(Qingxuedan) against 6-0HDA-induced toxicity in the primary culture of rat mesencephalic doperminergic neurons. Results : Chunghyul-dan(Qingxuedan) showed concentration-dependent scavenging activities in DPPH radical and ABTS cation scavenging assays and it was not cytotoxic to PC12 cells. In postand co-treatment, Chunghyul-dan(Qingxuedan) protected PC12 cells from the 6-OHDA induced toxicity at 50 and 100 ${\mu}$g/mL significantly. And Chunghyu!-dan(Qingxuedan) decreased the 6-OHDA induced ROS production at a dose dependent manner, while increaing the 6-OHDA induced GSH reduction at 50 and 100 ${\mu}$g/mL significantly. Finally, Chunghyul-dan(Qingxuedan) showed signicant protection of rat mescencephalic dopaminergic neurons from 6-OHDA at 1 ${\mu}$g/mL. Conclusions : These results demonstrate that Chunghyul-dan(Qingxuedan) has the antioxidant and neuroprotective effect against 6-0HDA induced cytotoxicity through decreasing ROS production and increasing GSH reduction.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.584-591
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• 2021

Marine algae (seaweed) encompass numerous groups of multicellular organisms with various shapes, sizes, and colors, and serve as important sources of natural bioactive substances. The brown alga Ecklonia cava Kjellman, an edible seaweed, contains many bioactives such as phlorotannins and fucoidans. Here, we evaluated the antioxidative, neuroprotective, and anti-apoptotic effects of E. cava extract (ECE), E. cava phlorotannin-rich extract (ECPE), and the phlorotannin dieckol on neuronal PC-12 cells. The antioxidant capacities of ECPE and ECE were 1,711.5 and 1,050.4 mg vitamin C equivalents/g in the ABTS assay and 704.0 and 474.6 mg vitamin C equivalents/g in the DPPH assay, respectively. The dieckol content of ECPE (58.99 mg/g) was approximately 60% higher than that of ECE (36.97 mg/g). Treatment of PC-12 cells with ECPE and ECE increased cell viability in a dose-dependent manner. Intracellular oxidative stress in PC-12 cells due to ECPE and ECE decreased dose-independently by up to 63% and 47%, respectively, compared with the stress control (323%). ECPE reduced the production of the pro-apoptotic proteins Bax and caspase-3 more effectively than ECE. Early and late apoptosis in PC-12 cells were more effectively decreased by ECPE than ECE treatments. From the results obtained in this study, we concluded that ECPE, which is rich in phlorotannins, including the marker compound dieckol, may be applied to the development of functional materials for improving cognition and memory.