• Toxicological Research
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• 제14권3호
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• pp.349-356
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• 1998

We identified S9940, a novel microbial metabolite from Streptomyces spp., to inhibit the release of neurotransmitter from PC12 cells. S9940 is an inhibitor of trifiated norepinephrine ([$^{3}H$]-NE) release in high $K^+$ buffer solution containing ionomycin, indicating that S9940 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. We also examined the effect of S9940 on $\beta-glucuronidase$ release from guinea pig neurophils and the effect on the neurite extension of PC12 cells and rat hippocampal neurons. As a result, S9940 inhibited $\beta-glucuronidase$ release: when treated with $5{\mu}g/ml$ of S9940, which prevented [$^{3}H$]-NE release, the inhibition of neurite extension for both PC12 cells and rat hippocampal neurons was observed.

• 생약학회지
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• 제30권1호
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• pp.79-83
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• 1999

The effects of coralyne, a protoberberine isoquinoline compound, on dopamine biosynthesis in PC12 cells were investigated. Coralyne decreased the dopamine content dose-dependently $(46.3%\;inhibition\;at\;20\;{\mu}M\;for\;24 hr).$ Dopamine content was lowered at 6 hr and reached minimal level at 24 hr after exposure to coralyne at $20\;{\mu}M.$ The decreased dopamine level was maintained up to 48 hr and recovered to the control level at about 72 hr. Tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine biosynthesis, was also inhibited at $20\;{\mu}M\;of\;coralyne$ by 16.1% relative to control. These results suggest that the inhibition of tyrosine hydroxylase by coralyne with a single treatment might be partially contributed to the decrease in dopamine content in PC12 cells.

• 약학회지
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• 제42권2호
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• pp.170-174
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• 1998

The effects of bulbocapnine, an aporphine isoquinoline alkaloid, on dopamine content in PC12 cells were investigated. Bulbocapnine decreased the dopamine content dose-dependentl y (39.2% inhibition at 2O${\mu}$M for 24 hr). The $IC_{50}$ value of bulbocapnine was 22.7${\mu}$M. Dopamine content was lowered at 6 hr after exposure to bulbocapnine. And then, the decreased dopamine level was almost maintained at 36 hr and recovered to the control level at about 60 hr. Tyrosine hydroxylase, the rate limiting enzyme in the catecholamine blosynthetic pathway, was also inhibited at 20${\mu}$M of bulbocapnine by 23.1% relative to control. We, therefore, hypothesized that the inhibition of tyrosine hydroxylase by bulbocapnine with a single treatment might be partially contributed to the decrease in dopamine content in PC12 cells.

• BMB Reports
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• 제41권6호
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• pp.479-484
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• 2008

In the present study, we demonstrate that ephrin-A5 is able to induce a transient increase of MAP kinase activity in PC12 cells. However, the effects of ephrin-A5 on the MAP kinase signaling pathway are about three-fold less than that of EGF. In addition, we demonstrate that EphA4 is the only Eph member expressed in PC12 cells, and that tyrosine phosphorylation induced by ephrin-A5 treatment is consistent with the magnitude and longevity of MAP kinase activation. Experiments using the Ras dominant negative mutant N17Ras reveal that Ras plays a pivotal role in ephrin-A5-induced MAP kinase activation in PC12 cells. Importantly, we found that the EphA4 receptor is rapidly internalized by endocytosis upon engagement of ephrin-A5, leading to a subsequent reduction in the MAP kinase activation. Together, these data suggest a novel regulatory mechanism of differential Ras-MAP kinase signaling kineticsexhibited by the forward signaling of EphA4 in PC12 cells.

• 한국식생활문화학회지
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• 제33권1호
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• pp.86-94
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• 2018

This study was designed to evaluate the antioxidant activities and protective effects on PC12 cells of the extract of Epimedium koreanum and its main constituents icariin and icariside I. After screening the seven identified flavonoid glycosides from E. koreanum through DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay, E. koreanum, Icariin and Icariside I exhibited significant effect on radical scavenging activity. E. koreanum, icariin and icariside I were examined using DPPH, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (ferric reducing ability power) assay. In all antioxidant assays, E. koreanum, icariin and icariside I showed high radical scavenging activities in a dose-dependent manner. Protective effects against $H_2O_2-induced$ PC12 cells were assessed with MTT assay. The results indicated that cell viability and protection on PC12 cells of icariside I and icariin increased dose dependently. These study results suggest that E. koreanum, icariin and icariside showed high antioxidant capacities and cell protective effects. Icariside I, one of the metabolites of icariin, may be a new and effective flavonoid compound as a functional component.

• 한방비만학회지
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• 제16권2호
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• pp.79-84
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• 2016

Objectives: The purpose of this study was to observe the effects of Citri Reticulatae Viride Pericarpium (CP) on 4-Hydroxynonenal (4-HNE)-induced inflammation in PC12 cells. Methods: 4-HNE was treated in PC12 cell to cause inflammatory response, and then treated with CP water extract at 25, 50, and $100{\mu}g/ml$. The phosphorylation of Jun N-terminal kinase (JNK) and the expression of $NF-{\kappa}B$ in PC12 cells were determined by Western blot, respectively. Results: The phosphorylation of JNK was significantly decreased in 4-HNE-stimulated PC12 cell by the treatment of CP extract at $25{\mu}g/ml$. The 4-HNE-induced expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) p65 in nuclear of the cells was significantly decreased in PC12 cell by treatment with CP extract at 25, 50, and $100{\mu}g/ml$. Conclusions: These results suggest that CP water extract has an anti-inflammatory activity through suppressing the JNK and $NF-{\kappa}B$ activation.

• 한국응용과학기술학회지
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• 제36권2호
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• pp.468-478
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• 2019

본 연구는 동충하초 추출물을 PC12 및 BV2 세포에서 인지능력 개선에 대한 효능을 평가하고자 하였다. 동충하초 추출물을 증류수로 추출하여 PC12 및 BV2 세포로 MTT 분석을 통해 세포 생존율을 확인하고 L-glutamate로 유도한 PC12 세포를 통해 세포 보호 효능과 아세틸콜린 함량 및 아세틸콜린에스테아제 활성을 평가하였다. 또한, LPS로 유도한 BV2 세포를 통해 nitric oxide (NO) 및 prostaglandin E2 (PGE2) 생성량 등의 항염증 효능을 측정하고 western blot 분석을 통해 $NK-{\kappa}B$, p38, JNK, caspase-3 등의 단백질 발현량을 확인하였다. 동충하초 추출물은 $200{\mu}g/m{\ell}$ 농도를 제외하고 1, 10, $100({\mu}g/m{\ell})$ 농도에서 세포 독성이 나타나지 않았다. L-glutamate로 유도한 PC12 세포에서 유의성있게 세포 보호 효능과 아세틸콜린 함량의 증가, 아세틸콜린에스테아제 활성 감소가 나타났다. 또한, 동충하초 추출물은 NO 및 PGE2 생성량과 $NK-{\kappa}B$, p38, JNK, caspase-3 등의 단백질 발현을 억제하였다. 이와 같은 결과는 동충하초 추출물이 인지능력에 대한 예방 및 개선 효능이 있음을 나타낸다. 따라서 동충하초 추출물은 인지능력 개선을 위한 새로운 천연 소재로 활용될 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제10권1호
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• pp.51-58
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• 2006

The promoting effect of hydrogen peroxide ($H_2O_2$) against the cytotoxicity of 1-methyl-4-phenylpyridinium ($MPP^+$) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with $MPP^+$ resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. Addition of $H_2O_2$ enhanced the $MPP^+-induced$ nuclear damage and cell death. Catalase, Carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the cytotoxic effect of $MPP^+$ in the presence of $H_2O_2$. Addition of $H_2O_2$ promoted the change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to $MPP^+$ in PC12 cells. The results show that the $H_2O_2$ treatment promotes the cytotoxicity of $MPP^+$ against PC12 cells. $H_2O_2$ may enhance the $MPP^+$-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that $H_2O_2$ as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by neurotoxins.

• 동의생리병리학회지
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• 제20권6호
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• pp.1459-1466
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• 2006

The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

• International Journal of Oral Biology
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• 제41권4호
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• pp.231-236
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• 2016

Inhibition of Rho-associated coiled coil-containing kinase (ROCK) has been reported to promote differentiation of neuronal cells. Here, we examined the effect of Y-27632, a ROCK inhibitor, on the outgrowth of neurites in PC12 cells. Y-27632 caused a rapid induction of neurite outgrowth in PC12 cells in a time-dependent manner. The neurite outgrowth, triggered by Y-27632, was accompanied by Rac1 activation, and was attenuated by Rac1 inhibitor NSC23766, in a concentration-dependent manner. Y-27632 also induced an increase in the production of reactive oxygen species (ROS). Pretreatment with N-acetylcysteine, an ROS scavenger, inhibited the ROS generation and neurite outgrowth in response to Y-27632. These results indicate that the activation of Rac1 and the generation of ROS contribute to the neurite outgrowth triggered by Y-27632 in PC12 cells.