• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1977-1981
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• 2012

Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with $IC_{50}$ of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway.

• 생명과학회지
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• 제22권8호
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• pp.1132-1136
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• 2012

많은 종류의 세포스트레스는 unfolded protein response (UPR)관련인자의 유전자발현을 조절한다. 본 연구결과 부동스트레스(immobilization stress)는 세포의 소포체스트레스(ER stress)와 관련된 유전자발현의 변화를 유도한다; Heart, spleen, thymus, kidney, testis에서는 유전자발현 변화가 없었지만 adrenal gland, liver, lung에서는 유의할만한 상승변화가 있었다. 그러나 muscle에서는 다른 것들과 대조적으로 발현이 감소되었다. 이 결과는 부동스트레스도 다른 종류의 세포스트레스와 같이 세포수준에서 UPR을 조절할 수 있다는 최초의 보고이다.

• Molecules and Cells
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• 제21권3호
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• pp.356-359
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• 2006

The transcription factor E2F1 coordinates cell cycle progression and induces apoptosis in response to DNA damage stress. Aside from DNA damage, the role of E2F1 in the endoplasmic reticulum (ER) stress signaling pathways is unclear. We found that $E2F1^{-/-}$ murine embryonic fibroblasts (MEFs) are resistant to apoptosis triggered by the ER stress inducer thapsigargin. In addition, E2F1 deficiency results in enhanced phosphorylation of eukaryotic translation initiation factor $2{\alpha}$ ($elF2{\alpha}$). These results therefore indicate that E2F1 deficiency increases phosphorylation of $elF2{\alpha}$ in response to ER stress triggered by thapsigargin, and suggest that the reduction in ER stress-induced apoptosis in E2F1-deficient cells is related to the high level of $elF2{\alpha}$ phosphorylation.

• Applied Microscopy
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• 제27권3호
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• pp.243-255
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• 1997

To investigate detoxification effects of aqua-acupuncture; Bovis Calculus and Susi Fei extract against the toxicity of aconitine were studied. We examined the GOT activities, GPT activities, $\gamma-GPT$ activites, ALP activities and ultrastructural changes of hepatocytes in rats. The GOT activities were decreased in the aqua-acupuncture group compared with control at the 48-hours and 96-hours. The $\gamma-GTP$ and ALP activities were decreased in the aqua-acpuncture group compared with control at 96-hours. We observed the ultrastructural changes of hepatocytes compared the detoxification effects of acua-acupuncture with toxicity of aconitine by transmission electron microscope. In the 24-hours group, the cisternae of rough and smooth endoplasmic reticulum hepatocytes are dilated more or less. In the 48-hours group, the nuclear envelope are irregured, and chromatins of nucleus are condensed. The cisternae of rough endoplasmic reticulum are dilated/branched. In the 96-hours group, the rough and smooth endoplasmic reticulum are well developed in aqua-acpuncture group compared with control. These results suggest that acua-acpuncture groups of the Bovis calculus and Susi fei extract showed detoxification effects against cytotoxicity of aconitine in the hepatocyte of rats.

• Genomics & Informatics
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• 제7권2호
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• pp.97-106
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• 2009

Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

• Clinical and Experimental Reproductive Medicine
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• 제42권1호
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• pp.1-7
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• 2015

Stress coping mechanisms are critical to minimize or overcome damage caused by ever changing environmental conditions. They are designed to promote cell survival. The unfolded protein response (UPR) pathway is mobilized in response to the accumulation of unfolded proteins, ultimately in order to regain endoplasmic reticulum (ER) homeostasis. Various elements of coping responses to ER stress including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been identified and were found to be inducible in oocytes and preimplantation embryos, suggesting that, as a normal part of the cellular adaptive mechanism, these coping responses, including the UPR, play a pivotal role in the development of preimplantation embryos. As such, the UPR-associated molecules and pathways may become useful markers for the potential diagnosis of stress conditions for preimplantation embryos. After implantation, ER stress-induced coping responses become physiologically important for a normal decidual response, placentation, and early organogenesis. Attenuation of ER stress coping responses by tauroursodeoxycholate and salubrinal was effective for prevention of cell death of cultured embryos. Further elucidation of new and relevant ER stress coping responses in periimplantation embryos might contribute to a comprehensive understanding of the regulation of normal development of embryonic development and potentiation of embryonic development in vitro.

• 한국동물학회지
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• 제20권2호
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• pp.101-107
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• 1977

토끼의 골격근 小胞體의 ATPase 活性과 Ca 輸送에 대한 sodium azide, cAMP, G-strophanthin 및 dicumarol의 영향을 측정하였다. Sodium azide(0.05mM)와 G-strophanthin(0.25nM)은 ATPase活性과 Ca 輸送能에 아무런 영향도 미치지 아니하였다. cAMP$(1 \\times 10^-6 M \\sim 5 \\times 10^-4 M)$는 ATPase 活性에는 아무런 영향도 미치지 않았으나 Ca 輸送은 억제하였다. Dicumarol(0.05mM)도 ATPase 活性에는 영향이 없었으나 小胞體의 $8,000 \\sim 12,000 \\times G$分劃에서의 Ca 輸送을 억제하였다.

• 생명과학회지
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• 제17권7호통권87호
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• pp.1023-1025
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• 2007

Ajuba is a number of proteins containing cytosolic LIM domain. Its function may provide a new pathway whereby cell-cell adhesive events are transmitted to the nucleus to regulate cell proliferation and differentiation decisions. Here, Ajuba gene expression was investigated its molecular properties associated with endoplasmic reticulum (ER) stresses (tunicamycin, DTT, A23187 and BFA) which induced remarkable ex-pression of Ajuba mRNA. The mRNA half life of Ajuba was also determined, its half life of Ajuba mRNA in FRTL-5 cells was approximately 2 hr after the initial translation. Although the obvious bioligical function of Ajuba is not clear, on the base of the results, Ajuba gene expression is deeply associated with ER stresses.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.41-47
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• 2019

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

• 한국동물학회지
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• 제28권2호
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• pp.85-98
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• 1985

종족발생학적 계통에 따른 소뇌에 대한 전자현미경적 연구의 일환으로서 발생과정이나 기능이 비슷한 무척추동물인 곤충강의 배추흰나비 (Pieris rapae Linne) 후뇌를 택하여 광학 및 전자현미경으로 관찰하였다. 본 실험의 성적에서는 배추흰나비의 후뇌에서 출현하는 세포를 각각의 미세구조, 즉 세포의 크기, 모습, 세포질의 많고 적음, 세포소기관의 발달 정도등을 기준으로 삼아 분류하였던 바 다음과 같은 결론을 얻었다. 배추흰나비의 후뇌에서는 세포층은 구분되지 않았고 각각 다른 6가지의 세포형을 구분하였다. 제I형 세포는 가장 큰 세포이며, 긴 난원형 내지 방추형인데 핵도 긴 난원형이었다. 핵의 염색질은 비교적 적으나 세포질 양은 월등히 많고 세포소기관도 발달되었는데 granular endoplasmic reticulum의 발달은 미약하였다. 제II형 세포는 방추형이나 그 크기는 I형보다 작고 핵의 염색질의 양은 역시 적었다. Granular endoplasmic reticulum을 비롯하여 세포소기관이 발달하였다. 제III형 세포는 둔 삼각형으로서 핵은 구형이며 제I형세포보다 크기가 작고 세포소기관이 비교적 발달하였으며 특히 mitochondria가 많으며 주변세포질에 filaments가 많이 출현하였다. 제IV형 세포는 난원형이며 그 크기나 세포소기관의 발달 정도가 제III형보다 미약하나 다량의 polysome을 포함하고 있었다. 제V형 세포는 대체로 난원형이지만 긴 세포질 돌기를 많이 가져서 불규칙한 모습이며 핵은 난원형으로서 염색질양은 적은 편이었다. 세포질 내의 소기관의 발달은 불량한 편이나 많은 polysome이 세포질 전반에 걸쳐 출현하였다. 제VI형 세포는 방추형이고 핵은 긴 난원형이며 세포 크기는 III형과 IV형의 중간에 해당하였다. 세포소기관의 발달은 대체로 미약하였으며 다수의 polysome과 소수의 granular endoplasmic reticulum 및 mitochondria가 있었고, 세포질 내에 이따금 유모성 물질이 출현하였다.