• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2371-2375
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• 2013

Breast cancer is one of the most common malignancies in women around the world. Among the various hormonal types of breast cancer, those that are estrogen receptor (ER) positive account for the majority. Among the estrogen related receptors, estrogen related receptor ${\alpha}$ is known to have a potential role in breast cancer and is one of the therapeutic target. Hence, prediction of novel ligands interact with estrogen related receptor alpha is therapeutically important. The present study, aims at prediction and analysis of ligands from the KEGG COMPOUND database (containing 10,739 entries) able to interact against estrogen receptor alpha using a similarity search and molecular docking approach.

• Environmental Analysis Health and Toxicology
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• 제20권3호
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• pp.249-258
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• 2005

Blood pressure, obesity and bone mineral density are multifactorial traits influenced by genetic factor. The purpose of this study was to clarify the association between three genetic polymorphisms in the estrogen receptor-$\alpha$ (ER -$\alpha$) gene and essential hypertension in korean population. One hundred and seventy-one people including 90 normotensives and 81 essential hypertentives were recruited. Among genetic polymorphisms studied, the Xba I RFLP in the intron 1 of this gene polymorphism was significantly associated with essential hypertension in women, suggesting the sexual dimorphism in genetic effect (P (<) 0.05). Further studied suggest that a larger sample size of this study are needed.

• 대한수의학회지
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• 제41권4호
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• pp.549-555
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• 2001

Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

• 대한의생명과학회지
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• 제25권1호
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• pp.23-31
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• 2019

The protein kinase $CK2{\alpha}$ (formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of $CK2{\alpha}$ activation in breast cancer have yet to be elucidated. This study investigated the mechanisms of $CK2{\alpha}$ activation in estrogen signaling. Estrogen increased reactive oxygen species (ROS) production, $CK2{\alpha}$ activity, and protein expression in estrogen receptor positive ($ER^+$) MCF-7 human breast cancer cells, which were inhibited by the antioxidant N-acetyl-L-cysteine. $H_2O_2$ enhanced $CK2{\alpha}$ activity and protein expression. Human epidermal growth factor (EGF) increased ROS production, $CK2{\alpha}$ activity and protein expression in EGF receptor 2 (HER2)-overexpressing MCF-7 (MCF-7 HER2) cells, but not in MCF-7 cells. Estrogen induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The p38 inhibitor, SB202190, blocked estrogen-induced increases in ROS production, $CK2{\alpha}$ activity and $CK2{\alpha}$ protein expression. The data suggest that ROS/p38 MAPK is the key inducer of $CK2{\alpha}$ activation in response to estrogen or EGF.

• 한국식품영양과학회지
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• 제44권7호
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• pp.993-999
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• 2015

본 연구에서는 선정한 생약재 및 복합처방단의 ${\alpha}$-glucosidase 저해 활성을 알아보았으며, 이 방법이 미백 소재 스크리닝을 위한 유용한 평가법인지를 알아보았다. 한의학과 민간에서 당뇨의 개선 및 치료 효과가 우수하다고 알려진 생약재 및 처방 중 죽력, 귀전우, 적양, 연자육, 마인, 청심연자음의 ${\alpha}$-glucosidase 활성 저해 효과는 식후 혈당조절제인 acarbose와 비교하여 볼 때 우수한 효과를 나타내었다. 미백 효과가 알려진 연자육을 함유한 청심연자음 hydrolyzed EtOAc layer는 $100{\mu}g/mL$ 농도에서 약 50% 멜라닌 생성 저해 효과를 보였다. 또한 청심연자음 hydrolyzed EtOAc layer는 ${\alpha}$-glucosidase 활성 저해 효과가 우수하였으나 mushroom tyrosinase 활성 저해 효과는 나타나지 않았다. 이로써 청심연자음 hydrolyzed EtOAc layer는 ${\alpha}$-glucosidase 활성을 저해시켜 tyrosinase의 glycosylation을 저해함으로써 멜라닌 생성 억제 효과가 나타나는 것으로 생각된다. 이상의 결과로 볼 때 ${\alpha}$-glucosidase 활성 억제 효과가 있으면서 당뇨병에 효과가 있는 생약재들은 N-linked glycoprotein인 tyrosinase의 glycosylation을 저해하여 tyrosinase의 세포 내 이동이나 활성을 억제함으로써 멜라닌 생성을 억제할 것으로 사료되며, 본 연구에서 선정된 생약재들은 당뇨병 치료를 위한 목적뿐만 아니라 화장품에서 새로운 미백 소재로서의 활용가치가 있을 것으로 판단된다. 또한 미백에 효과가 있는 소재 스크리닝을 위해 현재 널리 사용되고 있는 mushroom tyrosinase 활성 저해 효과와 다른 접근 방법으로써 ${\alpha}$-glucosidase 활성 측정 방법도 하나의 평가법으로 유용할 것으로 생각된다.

• 한국식품과학회지
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• 제51권4호
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• pp.361-368
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• 2019

황칠추출분말은 여성호르몬인 에스트로겐과 구조적 유사성을 가진 루틴을 다량 함유하고 있다(황칠추출분말 1g당 11.19 mg의 루틴 함유). 루틴은 식물성 여성호르몬이라고 불리는 플라보노이드 성분의 일종으로, 에스트로겐 수용체를 통한 신호전달을 증가시킨다. 특히 $ER-{\alpha}$로부터 세포내로 전달되는 MAPK/ERK 신호 전달 경로를 활성화시킴으로써, 갱년기의 대표적인 만성증상들을 개선할 수 있는 가능성이 있다고 여겨진다. 본 연구는 루틴이 다량 함유된 황칠추출분말을 폐경의 유도를 위해 난소를 절제한 쥐에 투여하여 여성갱년기 증상의 개선에 미치는 영향을 평가하였다. 그 결과 골교체율 관련 지표로서 폐경기 여성에서 높다고 알려진 오스테오칼신이 감소하는 경향성을 나타냈고, CTX는 유의적인 감소를 나타냈을 뿐만 아니라, 에스트로겐 수용체의 활성화를 증가시키는 경향성을 나타냈다. 이를 통해, 황칠추출분말은 골다공증의 예방 및 개선 효과를 나타내는 갱년기 여성 건강에 도움을 줄 수 있는 기능성 원료로서의 가능성을 보여준다.

• Asian-Australasian Journal of Animal Sciences
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• 제32권8호
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• pp.1095-1103
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• 2019

Objective: Among stress responses, the unfolded protein response (UPR) is a well-known mechanism related to endoplasmic reticulum (ER) stress. ER stress is induced by a variety of external and environmental factors such as starvation, ischemia, hypoxia, oxidative stress, and heat stress. Inositol requiring enzyme $1{\alpha}$ ($IRE1{\alpha}$)-X-box protein 1 (XBP1) is the most conserved pathway involved in the UPR and is the main component that mediates $IRE1{\alpha}$ signalling to downstream ER-associated degradation (ERAD)- or UPR-related genes. XBP1 is a transcription factor synthesised via a novel mechanism called 'frame switch splicing', and this process has not yet been studied in the horse XBP1 gene. Therefore, the aim of this study was to confirm the frame switch splicing of horse XBP1 and characterise its dynamics using Thoroughbred muscle cells exposed to heat stress. Methods: Primary horse muscle cells were used to investigate heat stress-induced frame switch splicing of horse XBP1. Frame switch splicing was confirmed by sequencing analysis. XBP1 amino acid sequences and promoter sequences of various species were aligned to confirm the sequence homology and to find conserved cis-acting elements, respectively. The expression of the potential XBP1 downstream genes were analysed by quantitative real-time polymerase chain reaction. Results: We confirmed that splicing of horse XBP1 mRNA was affected by the duration of thermal stress. Twenty-six nucleotides in the mRNA of XBP1 were deleted after heat stress. The protein sequence and the cis-regulatory elements on the promoter of horse XBP1 are highly conserved among the mammals. Induction of putative downstream genes of horse XBP1 was dependent on the duration of heat stress. We confirmed that both the mechanisms of XBP1 frame switch splicing and various binding elements found in downstream gene promoters are highly evolutionarily conserved. Conclusion: The frame switch splicing of horse XBP1 and its dynamics were highly conserved among species. These results facilitate studies of ER-stress in horse.

• Molecules and Cells
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• 제37권11호
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• 생명과학회지
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• 제27권2호
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• pp.233-240
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• 2017

본 연구는 소포체스트레스(endoplasmic reticulum stress)에 의해 유발되는 지방간(hepatic steatosis)에 대한 오미자추출물(Schisandra chinensis)의 주요성분인 gomisin A의 지방간 보호 효능에 대하여 연구하였다. 이를 위해 HepG2 세포에 소포체스트레스 유도물질인 tunicamycin 또는 palmitate을 처리하여 세포에서의 지방간 모델을 만들어 실험을 진행 하였으며, 소포체스트레스 표지자(marker)인 GRP78, CHOP, XBP-1의 발현을 측정하였다. Tunicamycin 처리한 세포에서는 GRP78, CHOP, XBP-1의 발현이 증가되었으나, gomisin A를 처리 한 세포에서는 이들의 발현 증가가 억제됨을 확인하였다. 이는 palmitate를 처리한 HepG2 세포에서도 palmitate에 의해 증가하는 소포체스트레스 표지자들이 gomisin A을 처리한 세포에서 발현이 감소함을 확인하였다. 이러한 결과에 의해, gomisin A는 소포체스트레스를 억제함을 알 수 있었다. 다음으로 gomisin A가 in vivo에서 소포체스트레스 및 지방간에 대한 보호효과가 있는지 확인하기 위해, tunicamycin과 고지방(high fat diet)으로 식이 한 쥐에서 소포체스트레스와 지방간의 보호효능에 대해 실험을 진행하였다. Tunicamycin과 고지방식이을 한 쥐의 간에서 중성지방이 증가하였으나, gomisin A를 처리한 쥐의 간에서 중성지방의 수준이 유의적으로 감소함을 확인하였다. 소포체스트레스 표지자들 역시 tunicamycin이나 고지방식이을 한 쥐에서 증가되나 gomisin A를 처리한 쥐에서 감소됨을 확인하였다. Gomisin A의 염증 반응에서의 조절기능을 확인하기 위하여 $TNF-{\alpha}$, IL-6 그리고 MCP1과 같은 염증관련 유전자들의 발현을 분석한 결과, tunicamycin이나 고지방식이을 한 쥐에서 염증유전자들의 발현이 증가하였으나 gomisin A를 처리한 쥐에서는 유의적으로 감소하였다. 종합적으로 본 연구 결과에 의하면, gomsin A는 소포체스트레스를 억제하여 지방간의 생성을 저해함을 알 수 있었다.

• Molecules and Cells
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• 제28권3호
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• pp.139-148
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• 2009

Cell death has been traditionally classified in apoptosis and necrosis. Apoptosis, known as programmed cell death, is an active form of cell death mechanism that is tightly regulated by multiple cellular signaling pathways and requires ATP for its appropriate process. Apoptotic death plays essential roles for successful development and maintenance of normal cellular homeostasis in mammalian. In contrast to apoptosis, necrosis is classically considered as a passive cell death process that occurs rather by accident in disastrous conditions, is not required for energy and eventually induces inflammation. Regardless of different characteristics between apoptosis and necrosis, it has been well defined that both are responsible for a wide range of human diseases. Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-${\alpha}$ ($G6Pase-{\alpha}$) or glucose-6-phosphate transporter (G6PT) responsible for glucose homeostasis, leading to GSD-Ia or GSD-Ib, respectively. This review summarizes cell deaths in GSD-I and mostly focuses on current knowledge of the neutrophil apoptosis in GSD-Ib based upon ER stress and redox signaling.