• Applied Microscopy
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• v.3 no.1
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• pp.17-22
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• 1973

The author studied ed the effect of ethionine upon the absorption epithelium of ileum with particular ettention to the endoplasmic reticulum. Five tenth per cent of DL-ethionine was added to the diet of the experimental group rats and they were sacrificed after 1, 2, 3, and 4 weeks. respectively. The ileum were observed by the electron microscope. The results obtained were summarized as follow: The changes were detachment of membrane bound ribosome, dilatation of endoplasmic reticulum, decrease of polysome with reciprocal increase of monosome, and dilatation of Golgi complex. These changes were occured at 2 nd to 3 rd week from start of ethionine feeding and more severe at fouth week. These observation suggested that ethionine induced degenerative changes of the organelles.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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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.

• Journal of Life Science
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• v.22 no.8
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• pp.1132-1136
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• 2012

Many kind of cell stresses induce gene expression of unfolded protein response (UPR)-associated factors. This study demonstrated that up- and down-regulation of gene expression of endoplasmic reticulum (ER) stress chaperones and ER stress sensors was induced by immobilization stress in the rat organs (adrenal gland, liver, lung, muscle). However, no statistically significant regulation was detected in the others (heart, spleen, thymus, kidney, testis). The results are the first to show that immobilization stress induces UPR associated gene expression, will help to explain immobilization stress-associated ER stress.

• Molecules and Cells
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• v.21 no.3
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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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• v.27 no.3
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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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• v.7 no.2
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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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• v.42 no.1
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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.

• Biomolecules & Therapeutics
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• v.27 no.1
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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.

• Biomedical Science Letters
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• v.13 no.2
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• pp.153-155
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• 2007

Ferritin heavy chain 1 (FTH1) is an ubiquitous and highly conserved protein which plays a major role in iron homeostasis. The expression of FTH1 was specifically enhanced under various condition of endoplasmic reticulum (ER) stresses drugs such as Brefeldin A (BFA), DTT (Dithiothreitol), calcium ionophore A23187 and tunicamycin. We firstly report here that ER-stress induces up-regulated expression of FTH1 in FRTL-5 culture thyrocytes.

• The Korean Journal of Zoology
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• v.28 no.2
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• pp.85-98
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• 1985

The present study was carried out light and electron microscopic analysis of the structures of the tritocerebral neurons in butterfly (Pieris rapae Linne) from Insecta. We have summarized our morphological analyses as follows: In insecta, tritocerebrum of butterfly shows tentatively classified 6 neuronal types without any arrangement of cell layers. Type I cells with long oval or spindle shape are the largest out of 6 kinds. The nucleus contains a small amount of chromatin. In the large volume of cytoplasm there contained rich cell organelles except granular endoplasmic reticulum. Type II cells are smaller than type I neurons, but their ultrastructural features are similar to type I neuron. They have well-developed granular endoplasmic reticulum. Type III cells are spherical or triangular and smaller than type I neuron with spherical nuclei. Cell organelles are mostly prominent, esp., mitochondria, ribosomes and fine fibrils which are arranged in periphery of the cytoplasm.