• 생명과학회지
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• 제13권3호
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• pp.248-251
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• 2003

갑상선호르몬의 전구체인 thyroglobulin (Tg)이 어떻게 dimerization이 일어나는지를 조사하였다, 변성 혹은 비변성전기영동법으로 관찰한 결과 새롭게 만들어지기 시작한 Tg는 15분에 처음으로 구조적으로 불안정하지만 folded monomer가 관찰되었다. 그 이후에 monomer가 dimer로 바뀌어 결국 30분에 dimer Tg가 만들어지기 시작하여 40분에는 dimer Tg가 관찰되었다. 최종적으로 60분에 완전하게 dimerization된 Tg가 만들어졌다.

• Molecules and Cells
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• 제44권8호
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• pp.569-579
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• 2021

Cyclase-associated protein 2 (CAP2) has been addressed as a candidate biomarker in various cancer types. Previously, we have shown that CAP2 is expressed during multi-step hepatocarcinogenesis; however, its underlying mechanisms in liver cancer cells are not fully elucidated yet. Here, we demonstrated that endoplasmic reticulum (ER) stress induced CAP2 expression, and which promoted migration and invasion of liver cancer cells. We also found that the ER stress-induced CAP2 expression is mediated through activation of protein kinase C epsilon (PKCε) and the promotor binding of activating transcription factor 2 (ATF2). In addition, we further demonstrated that CAP2 expression promoted epithelial-mesenchymal transition (EMT) through activation of Rac1 and ERK. In conclusion, we suggest that ER stress induces CAP2 expression promoting EMT in liver cancer cells. Our results shed light on the novel functions of CAP2 in the metastatic process of liver cancer cells.

• IMMUNE NETWORK
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• 제12권5호
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• pp.189-195
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• 2012

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanisms are still largely unknown. The incidence of colon cancer is now increasing in Korea. Therefore, we have examined here the effect of vitamin C on the induction of the apoptosis on colon cancer and its related mechanisms. We have found that remarkable increase of the apoptosis and the calcium influx in endoplasmic reticulum (ER) in human colon cancer cell line, HCT-8. However, vitamin C-induced apoptosis was effectively inhibited by the pre-treatment of BAPTA-AM (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), which is well-known as a calcium specific chelator. During the apoptosis, we found the increase of the translocation of Bad to mitochondria from cytosol, after releasing from 14-3-$3{\beta}$. In this process, the expression of Bax, a well-known pro-apoptotic protein, was also increased. Taken together, vitamin C induces apoptosis of colon cancer cell line, HCT-8 through the increase of 1) the calcium influx in endoplasmic reticulum (ER), 2) the translocation of Bad to mitochondria, and 3) the expression of Bax.

• KSBB Journal
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• 제13권4호
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• pp.369-377
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• 1998

To analyze the unique aspects of biomolecular processing for monoclonal antibody (MAb) production and secretion, the simple working model based on 3-compartment (endoplasmic reticulum, Golgi apparatus, and extracellular medium) was developed. Based on in vitro MAb assembly experimental results, the kinetic model for MAb assembly in the endoplasmic reticulumn was proposed. The dynamics of MAb assembly and secretion was simulated using methematica program. According to the simulation results, the proposed 3-compartment model provides an efficient means to predict the specific MAb productivity as well as intracompartmental concentrations of MAb in endoplasmic reticulum, Golgi apparatus, and extracellular compartment model. In vivo profiles of MAb intermediates gave good agreements with the simulation profiles predicted by the intracellular compartment model. Furthermore, results of such analysis can help in directing the control strategy for optimum biomolecular processing in a mammalian cell culture system.

• Applied Microscopy
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• 제31권4호
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• pp.347-354
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• 2001

완두 종자 발달의 이른 시기에 특징적으로 조면 소포체 내강에 단백질이 축적되는데 이 단백질에 대한 전자현미경적 면역세포 화학적 반응을 실시한 결과 legumin으로 확인되었다. 이 단백질은 소포체 내강에 점점 축적되고 소포체 끝이 부풀어서 단백과립으로 발달하였다. 완두의 단백과립 발달 과정은 3가지 유형이 확인 되었는데, 단백질 저장 액포의 분절에 의해서 형성된 제 1형 단백과립, 가장자리에 단백질이 축적된 단백질 저장 액포의 budding에 의해서 형성된 제 2 형 단백과립, 그리고 단백질 저장 소포체의 끝이 부풀어서 형성된 제 3형 단백과립으로 구분되었다. 제 3형 단백과립은 수정 후 $23\sim25$일 사이의 짧은 기간에 급격하게 발달되어 자엽세포를 가득차게 만드는 것으로 확인 되었으며, 이러한 유형은 지금까지 알려지지 않은 새로운 단백과립 발달과정으로 생각된다.

• Applied Microscopy
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• 제36권4호
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• pp.291-297
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• 2006

주류의 섭취가 산업화학물질의 생체 내 독성유발에 어떠한 영향을 미치는지를 검토하기 위해 흰쥐를 이용하여 15%에탄올을 6주간 섭취시킨 후, cyclohexane(CH)을 2일 간격으로 4회 복강 투여하고 24시간 후 다음과 같은 결과를 얻었다. CH의 투여로 인해 정상군과 비교하여 간 무게와 헐청내 xanthine oxidase활성은 증가되었고, 간 내 glucose-6-phosphatase활성은 감소되었다. 그리고 CH 대사효소인 cytochrome P450 dependent aniline hydroxylase와 alcohol dehydrogenase의 활성은 CH투여 후 유의적으로 증가되었으며, 알코올 전처치 후 CH투여군이 가장 높은 활성을 보였다. 미세구조적으로도 알코올 섭취군과 CH투여군 모두에서 조면소포체로부터 활면소포체로의 전환이 일어났으며, 전 실험군 중 알코올 전처치 후 CH투여군이 가장 높은 전환율을 보였다. 이러한 결과들로 볼 때, 병변을 초래하지 않는 수준의 알코올의 섭취는 CH대사활성을 증대시키는 것으로 판단되었다.

• Applied Microscopy
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• 제32권2호
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• pp.149-156
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• 2002

본 연구는 흰쥐의 간장에서 납 독성에 대한 활성탄 효과를 연구하는데 그 목적이 있다. 실험동물은 $7{\sim}8$주된 150 g 내외의 Sparague-Dewley계 웅성 Rat를 사용하였다. lead acetate (500 ppm)를 1주 2회 복강 투여하였고 활성탄(40 mg/kg)을 1일/1회씩 경구투여하여 4주, 8주째에 간장을 적출해서 투과전자현미경으로 관찰한 바 다음과 같은 결과를 얻었다. 납 단독투여 4주군은 과립형질내세망의 수조가 팽대되고, 리보솜의 탈락이 관찰되었다. 핵은 약간 함입되어 불규칙하였으며 핵막은 팽대되어 내외막과 핵공이 불분명하게 나타났다. 납-활성탄 투여 4주군은 과립형질내세망은 리보솜이 부착된 정상적인형태로 관찰되었다. 다수의 리소좀이 관찰되었다. 핵은 둥근 형태로 관찰되었다. 납 단독투여 8주군은 과립형질내세망의 수조가 더욱 심하게 팽대되어 공포화를 나타냈다. 사립체는 더욱 팽창되서 사립체능이 절단, 손실되어 낮은 전자밀도를 나타냈다. 핵은 약간 함입되어 불규칙하고 핵막이 팽대되었다. 납-활성탄 투여 8주군은 일부 과립형질내세망의 수조가 팽대되었으나 리보솜이 부착된 정상적인 형태로 핵 주위에 전형적인 층판구조를 형성하였다. 사립체는 약간 팽창되었고, 핵은 정상으로 보였다.

• Molecules and Cells
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• 제38권10호
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• pp.851-858
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• 2015

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

• Journal of Nutrition and Health
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• 제45권5호
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• pp.420-428
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• 2012

The purpose of this study is to investigate the effects of eight weeks high fat intake and regular exercise in skeletal muscle and adipose tissue for Endoplasmic Reticulum (ER) stress in rats. This experiment involved 32 subjects (sprague-dawley rats) divided into four groups as follows: chow group (Chow, n = 8), chow and exercise group (Chow + EX, n = 8), high fat diet-induced hyperlipidemia group (HF, n = 8), and HF and exercise group (HF + EX, n = 8). As a result, there were significant decrease in body weight and abdominal fat, and blood lipid level was significantly improved by exercise for eight weeks (p < .05). There were variables changed about the skeletal muscle and ER stress in GRP78, XBP-1, ATF4, CHOP and JNK mRNA. There increased in mRNA factor by exercise, especially GRP78, and ATF4 mRNA were significantly increased in exercise (p < .05). However, there were increased in adipose tissue by exercise and there were significantly decreased in mRNA factor by high fat diet (p < .05). Consequently, this study suggests that the consistent exercise was more improved of obesity factor, such as dyslipidemia, hyperlipidemia, hyperglycemia, as well as body weight or abdominal fat. The response of ER stress in adipose tissue and skeletal muscle were more sensitive in exercise than high fat diet feed.

• Journal of Nutrition and Health
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• 제52권2호
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• pp.176-184
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• 2019

Purpose: Protein overloading in the endoplasmic reticulum (ER) leads to endoplasmic reticulum stress, which exacerbates various disease conditions. Emodin, an anthraquinone compound, is known to have several health benefits. The effect of emodin against palmitic acid (PA) - induced ER stress in HepG2 cells was investigated. Methods: HepG2 cells were treated with varying concentrations of palmitic acid to determine the working concentration that induced ER stress. ER stress associated genes such as ATF4, XBP1s, CHOP and GRP78 were checked using RT- PCR. In addition, the expression levels of unfolded protein response (UPR) associated proteins such as $IRE1{\alpha}$, $eIF2{\alpha}$ and CHOP were checked using immunoblotting to confirm the induction of ER stress. The effect of emodin on ER stress was analyzed by treating HepG2 cells with $750{\mu}M$ palmitic acid and varying concentrations of emodin, then analyzing the expression of UPR associated genes. Results: It was evident from the mRNA and protein expression results that palmitic acid significantly increased the expression of UPR associated genes and thereby induced ER stress. Subsequent treatment with emodin reduced the mRNA expression of ATF4, GRP78, and XBP1s. Furthermore, the protein levels of $p-IRE1{\alpha}$, $p-eIF2{\alpha}$ and CHOP were also reduced by the treatment of emodin. Analysis of sirtuin mRNA expression showed that emodin increased the levels of SIRT4 and SIRT7, indicating a possible role in decreasing the expression of UPR-related genes. Conclusion: Altogether, the results suggest that emodin could exert a protective effect against fatty acid-induced ER stress and could be an agent for the management of various ER stress related diseases.