• 동의생리병리학회지
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• 제38권1호
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• pp.38-45
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• 2024

To compare and analyze the improvement effects of white ginseng extract, red ginseng extract, and black ginseng extract on cognitive dysfunction and memory impairment caused by scopolamine in rats. In the cognitive behavioral test, the tendency of the SCOP+B group to overcome the escape time delay induced by scopolamine administration was observed, unlike the SCOP group. The frequency on plat form was significantly increased in the group treated with ginseng extracts compared to the SCOP group. As a result of measuring the duration time on goal quadrant, the time spent in the quadrant was significantly increased in the SCOP+B group compared to the SCOP group. In the hippocampus, the SCOP-treated group significantly decreased the activity of AChE compared to the normal group, but the ginseng extract-treated groups significantly increased it compared to the SCOP group. After sacrificing the rats after the behavioral test, the expression of PSD95 protein in the excised brain was significantly decreased in the SCOP group compared to normal, but it was observed that the SCOP+R and SCOP+B groups were significantly increased compared to the SCOP group. CREB1 protein expression was significantly increased in the SCOP+R group, and the expression of Cdk5 was significantly increased in the SCOP+B group. Ginseng extracts significantly restored the memory damaged by scopolamine suggesting that red ginseng increased the expression of CREB1 and PSD95 proteins, and black ginseng increased the protein expression of Cdk5 and PSD95 to induce memory recovery.

• BMB Reports
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• 제41권7호
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• pp.523-528
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• 2008

BMI-1026 is a synthetic aminopyrimidine compound that targets cyclin dependent kinases (cdks) and was initially designed as a potential anticancer drug. Even though it has been well documented that BMI-1026 is a potent cdk inhibitor, little is known about the cellular effects of this compound. In this study, we examined the effects of BMI-1026 treatment on inducing premature senescence and then evaluated the biochemical features of BMI-1026-induced premature senescence. From these experiments we determined that BMI-1026 treatment produced several biochemical features of premature senescence and also stimulated expression of mitogen activated protein kinase (MAPK) family proteins. BMI-1026 treatment caused nuclear translocation of activated Erk1/2 and the formation of senescence associated heterochromatin foci in 5 days. The heterochromatin foci formation was perturbed by inhibition of Erk1/2 activation.

• BMB Reports
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• 제43권10호
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• pp.704-709
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• 2010

The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase $3\beta$(GSK-3$\beta$), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis.

• 생명과학회지
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• 제19권5호
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• pp.620-624
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• 2009

동면 개시인자로 알려진 DADLE는 여러 연구에 의해 in vivo와 in vitro 상에서 유사 동면 상태를 야기한다. 본 연구는 인체혈구암세포인 U937 세포주의 세포 사멸과 세포 주기 둥에 대한 DADLE의 영향을 살펴보았다. DADLE가 처리된 U937세포는 8${\sim}6$10 ${\mu}$M의 높은 농도에서 세포 증식이 감소하였으며, 0${\sim}6$ ${\mu}$M의 낮은 농도에서 영향이 없었다. DNA flow cytometer를 이용하여 세포 주기를 분석해본 결과 DADLE에 의한 세포 주기 억제가 관찰되었다. DADLE처리에 따른 세포 증식률 감소 및 세포 주기 억제효과를 전사 수준에서 조사한 결과 Bcl-XL, c-IAP-2의 발현 및 survivin의 발현 감소가 관찰되었으며, COX-2의 발현 역시 COX-1의 변화 없이 감소함을 확인하였다. 또한, cyclin E 와 cdk-2, -4 그리고 -6의 발현 역시 감소하는 것을 관찰하였다. Telomere 조절 관련 유전자의 경우도 c-myc과 TERT의 감소, 그리고 TEP-1가 증가하는 현상을 관찰하였다. 이상의 결과는 DADLE를 U937 암세포주에 처리했을 때 세포 주기의 억제를 통하여 life-time을 증가시킬 가능성을 시사하며 이에 관한 지속적인 연구가 필요할 것으로 사료된다.

• 생명과학회지
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• 제23권5호
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• pp.622-628
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• 2013

본 연구에서는 마늘에서 유래된 생리활성 물질인 diallyl trisulfide (DATS) 처리에 따른 U937 인체혈구암세포의 증식억제가 apoptosis 및 cell cycle arrest 유발과 관련이 있는지 조사하였다. U937 세포증식은 DATS에 의해 농도 및 시간 의존적으로 감소함을 확인 하였고, 이는 apoptosis에 의한 직접적인 세포죽음과 CDK1 및 cyclin B1의 발현 증가 및 histone H3의 인산화와 연관된 mitotic arrest와 관련이 있음을 알 수 있었다. 또한 DATS 처리 초기에 reactive oxygen species (ROS)의 생성이 매우 증가되었으나, ROS scavenger (N-acetyl-l-cysteine)에 의한 인위적 ROS 생성의 억제는 DATS에 의한 apoptosis 및 mitotic arrest를 완벽하게 차단시켰다. 이는 U937 세포에서 DATS에 의해 유도된 apoptosis 및 mitotic arrest가 ROS에 의해 매개된다는 것을 의미하며, 본 연구의 결과는 DATS가 인체혈구암세포에서 세포증식억제와 관련된 항암기전을 이해할 수 있는 기초자료로서 매우 유용하게 사용될 것이라 생각된다.

• Animal Bioscience
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• 제35권7호
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• 한국식품영양과학회지
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• 제33권1호
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• pp.1-6
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• 2004

$\beta$-Sitosterol은 과일과 야채 등을 포함한 대부분의 고등식물에 존재하는 중요한 phytosterol의 하나로서, 인체 암의 예방과 치료에 매우 유효한 것으로 보고되어져 오고 있다. 본 연구에서는 $\beta$-sitosterol의 암세포 증식억제 기전의 해석을 시도하기 위하여 인체 대장암세포 HCT116의 증식에 미치는 $\beta$-sitosterol의 영향을 조사하였다. $\beta$-Sitosterol의 처리로 HCT116 암세포의 증식은 처리 농도 의존적으로 감소되었으며, 특히 7.5 $\mu$M 이상 처리에서는 급격한 성장억제 효과가 있었다. 또한 5.0 $\mu$M 처리군에서부터 apoptotic body의 형성이 관찰되었고, $\beta$-catenin 단백질의 분해 현상과 연관성이 있었다. 그리고 $\beta$-sitosterol이 처리된 암세포에서는 종양억제유전자 p53 및 Cdk inhibitor p21의 발현이 전사 및 번역 수준에서 모두 증가되었다. 본 결과는 그동안 연구가 거의 진행되어져 있지 않았던 $\beta$-sitosterol에 의한 암세포주기 조절 해석을 위한 주요한 자료로 활용될 것이다.

• 한국임상약학회지
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• 제30권1호
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• pp.1-10
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• 2020

Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.203-208
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• 2013

As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

• Journal of Yeungnam Medical Science
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• 제22권2호
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• pp.166-182
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• 2005

정상인의 말초혈액 림프구 DNA를 주형으로 사용하여 DNA PCR을 시행하였다. 그 결과 5례 모두에서 예상되는 167bp 크기의 CDKN2 genomic DNA 단편이 증폭됨을 관찰할 수 있었다. 정상인의 말초혈액 림프구로부터 분리한 mRNA를 사용하여 cDNA를 합성하고 이를 주형으로 사용하여 RT-PCR와 시행하였다. 그 결과 예상되는 355bp 및 468bp의 CDKN2 및 ${\alpha}$-actin의 mRNA 전사산물이 전례에서 발현됨을 관찰할 수 있었다. 또한 CDKN2 mRNA의 RT-PCR 산물을 Sal I 제한효소로 절단하여 252bp와 103bp의 두 단편으로 나뉘어짐을 관찰하였다. 총 5례의 후두 편평상피세포암 세포주에서 CDKN2가 발현되는지를 RT-PCR로 관찰하였으며 각 세포주로부터 mRNA의 분리가 잘되었는지는 ${\alpha}$-actin의 발현을 통하여 RT-PCR로 관찰하였다. 5례의 세포주에서 모두 ${\alpha}$-actin의 발현을 관찰할 수 있었으며 이들의 mRNA를 사용하여 CDKN2 RT-PCR와 시행한 결과 총 4례(80%)의 세포주에서 CDKN2의 발현이 상실되어 있음을 알 수 있었다. CDKN2 발현의 이상이 있는 후두 편평상피세포암 세포주 및 발현이 정상인 후두 편평상피 세포암 세포주 모두에서 CDKN2 유전자의 존재를 DNA-PCR로 관찰하여 총 5례의 세포주 중 2례(40%)에서 CDKN2 유전자의 결손을 관찰할 수 있었다. 이 2례의 후두 편평상피세포암 세포주는 CDKN2의 발현이 일어나지 않은 것으로 RT-PCR의 결과와 일치하였다. 총 8례의 후두 편평상피세포암세포들에서 CDKN2의 이종접합성의 상실이 발견되는지를 DNA-PCR로 관찰하여 7례(87.5%)에서 최소한 한 개 이상의 microsatellite marker에 대한 이종접합성의 상실이 발견되었으며, 6례(75%)에서 최소한 한 개 이상의 microsatellite marker에 대한 증폭이 발견되었다. 또한 2례에서 최소한 한 개 이상의 microsatellite marker에 대한 microsatellite의 불안정이 발견되었다. 이종접합성의 상실, 증폭 또는 microsatellite의 불안정의 세 가지 모두를 보면 전례에서 한가지 이상의 CDKN2의 이상이 발견되었다. 이상의 결과로 볼 때 CDKN2가 후두암의 발생에 중요한 역할을 하고 있을 것으로 사료된다.