• The Korean Journal of Physiology and Pharmacology
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• 제7권1호
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• pp.33-37
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• 2003

Oxidative damage to mitochondria is a critical mechanism in necrotic or apoptotic cell death induced by many kinds of toxic chemicals. Thioredoxin (Trx) family proteins are known to play protective roles in organisms under oxidative stress through redox reaction by using reducing equivalents of cysteines at a conserved active site, Cys-X-X-Cys. Whereas biological and physiological properties of Trx1 are well characterized, significance of mitochondrial thioredoxin (Trx2) is not well known. Therefore, we addressed physiological role of Trx2 in PC12 cells under oxidative stress. In PC12 cells, transiently overexpressed Trx2 significantly reduced cell death induced by hydrogen peroxide, whereas mutant Trx2, having serine residues instead of two cysteine residues at the active site did not. In addition, stably expressed Trx2 protected PC12 cells from serum deprivation. These results suggest that Trx2 may play defensive roles in PC12 cells by reducing oxidative stress to mitochondria.

• BMB Reports
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• 제47권8호
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• pp.424-432
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• 2014

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.

• Journal of Microbiology and Biotechnology
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• 제25권2호
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• pp.302-306
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• 2015

VvpM, one of the extracellular metalloproteases produced by Vibrio vulnificus, induces apoptotic cell death via a pathway consisting of ERK activation, cytochrome c release, and activation of caspases-9 and -3. VvpM-treated cells also showed necrotic cell death as stained by propidium iodide (PI). The percentage of PI-stained cells was decreased by pretreatment with Necrostatin-1, indicating that VvpM-mediated cell death occurs through necroptosis. The appearance of autophagic vesicles and lipidated form of light-chain-3B in rVvpM-treated cells suggests an involvement of autophagy in this process. Therefore, the multifarious action of VvpM might be one of the factors responsible for V. vulnificus pathogenesis.

• BMB Reports
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• 제51권5호
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• The Plant Pathology Journal
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• 제32권4호
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• pp.311-320
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• 2016

Xanthomonas axonopodis pv. glycines (Xag) is a necrotrophic bacterial pathogen of the soybean that causes bacterial pustules and is a nonhost pathogen of the chili pepper. In the current study, chili pepper fruit wound inoculated in planta with Xag 8ra formed necrotic lesions on the fruit surface and induced several structural and chemical barriers systemically in the fruit tissue. The initial defense response included programmed cell death of necrotizing and necrotized cells, which was characterized by nuclear DNA cleavage, as detected by TUNEL-confocal laser scanning microscopy (CLSM), and phosphatidylserine exposure on cell walls distal to the infection site, as detected by Annexin V FLUOS-CLSM. These two responses may facilitate cell killing and enhance transportation of cell wall materials used for cell wall thickening, respectively. The cells beneath the necrotic tissue were enlarged and divided to form periclinal cell walls, resulting in extensive formation of several parallel boundary layers at the later stages of infection, accompanying the deposition of wall fortification materials for strengthening structural defenses. These results suggest that nonhost resistance of chili pepper fruit against the nonhost necrotrophic pathogen Xag 8ra is activated systematically from the initial infection until termination of the infection cycle, resulting in complete inhibition of bacterial pathogenesis by utilizing organspecific in situ physiological events governed by the expression of genes in the plant fruit organ.

• 대한수의학회지
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• 제37권1호
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• pp.161-166
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• 1997

From January of 1991 to December of 1992, 42 chickens collected from 21 poultry farms and also diagnosed as necrotic enteritis(NE) was examined clinical signs, gross and histopathological findings. Main clinical signs were characterized by decreased appetite, mild to severe depression, reductance to move, ruffled feathers, greenish to yellow-browinish diarrhea sometimes including blood. As progressed, diseased chickens showed feces mixed with necrotic debris which detached from the intestinal mucosa and mostly resulted in the death. In chronic cases, there were dirty feathers around cloaca due to diarrhea and notably retarded growth. Principle gross lesions were usually confined to the jejunum and ileum, especially toward the lower part of Meckel's diverticulum. The part of small intestine was frequently distended with gas, and also showed mucosal congestion and hemorrhages with varying degrees. Sometimes, the intestinal mucosa was thickened, and also covered with fibronecrotic psuedomembrane. In addition, there were focal necrosis and severely multifocal ulcreation in the mucosa of small intestine. Major histopathological findings included villous necrosis and erosion of the small intestine covering with lots of bacterial colonies, inflammatory cell infiltration in the lamina propria, and dilatation and hyperplasia of crypts. Luminal exudate contained bacterial colonies, fibrin, erythrocytes, and desquamated epithelium. Thirteen(61.9%) out of 21 NE-occurring farms were complicated with intestinal coccidiosis.

• Applied Microscopy
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• 제37권4호
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• pp.239-248
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• 2007

암세포가 있는 장소의 온도를 변화시키는 것은 하나의 암 치료 방법이 될 수 있다. 명확한 기전은 아직 잘 밝혀져 있지 않지만, 고온은 미토콘드리아로 신호를 전달해서 cytochrome c를 분비시키는 세포자멸사로의 길로 유도하는 것으로 알려져 있다. 저온은 $30^{\circ}C$ 미만에서 세포자멸사를 유도하지만 심하지 않은 저온에서는($35{\sim}33^{\circ}C$ 혹은 $31{\sim}29^{\circ}C$)오히려 세포자멸사를 막는 것으로 알려져 있다. CC-t6와 GB-d1세포 주는 림프절로 전이된 사람의 담관암과 담낭암에서 확립한 것으로, 이와 같은 전이성 암세포가 온도 변화에 어떻게 반응을 하는지를 연구하기 위해 고온노출($37{\rightarrow}43^{\circ}C$)과 저온노출($37{\rightarrow}17.4^{\circ}C$)을 시행하였다. 세포의 종류나 온도 변화를 통한 스트레스의 방법과 관계없이 죽는 세포가 관찰되었으며, 고온노출이 가장 심한 영향을 주었다. 이런 죽어가는 세포는 세포자멸사가 아닌 세포괴사의 경로를 거치고 있었다. 투과전자현미경을 이용한 관찰에서 세포자멸사적인 모습은 보이지 않았고, caspase-3, -9, cytochrome c, Bax 같은 세포자멸사와 관련된 단백질의 변화도 관찰되지 않았고, 열충격단백질 70과 27도 증가하였다. 결국 CC-t6와 GB-d1 세포는 온도변화를 통한 스트레스를 주었을 경우 세포괴사로 죽음을 알 수 있었다. 온도변화를 통한 스트레스는 열충격단백질의 증가와 함께 세포괴사를 일으켰다. GB-d1과 CC-t6 세포에서 고온은 가장 심각하게 세포괴사를 일으켰으며, 저온은 초기에는 세포괴사를 유발하였으나 12시간 경과후에는 세포분열이 더욱 활발하게 일어나 세포의 생명력을 연장시켜주었다. 결국 이 실험에서는 전이성 암세포를 제거하는 방법으로는 고은이 가장 효과적이며 유용함을 알 수 있었다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권6호
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• pp.564-570
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• 2005

In the present study, the protective effects of Bcl-2 over-expression in a suspension culture (without any adaptation) and spent medium (low nutrient and high toxic metabolite conditions) were investigated. In the suspension culture without prior adaptation, the viability of the control cell line fall to 0% by day 7, whereas the Bcl-2 cell line had a viability of 65%. The difference in the viability and viable cell density between the Bcl-2 and control cell lines was more apparent in the suspension culture than the static culture, and became even more apparent on day 6. Fluorescence microscopic counting revealed that the major mechanism of cell death in the control cell line in both the static and suspension cultures was apoptosis. For the Bcl-2 cell lines, necrosis was the major mode of cell death in the static culture, but apoptosis became equally important in the suspension culture. When the NS0 6A1 cell line was cultured in spent medium taken from a 14 day batch culture, the control cell line almost completely lost its viability by day 5, whereas, the Bcl-2 still had a viability of 73%. The viable cell density and viability of the Bcl-2 cell line cultivated in fresh medium were 2.2 and 2.7 fold higher, respectively, than those of the control cultures. However, the viable cell density and viability of the Bcl-2 cultivated in the spent medium were 8.7 and 7.8 fold higher, respectively, than those of the control cultures. Most of the dead cells in the control cell line were apoptotic; whereas, the major cell death mechanisms in the Bcl-2 cell line were necrotic.

• 대한한의학회지
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• 제26권2호
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• pp.63-76
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• 2005

Objectives: Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide range of acute and longterm neurodegenerative diseases. This study was undertaken to examine whether Sunghyangchungisan(SHCS), a well-known prescription in Korean traditional medicine, might have beneficial effects on ROS-induced brain cell injury. Methods: Human neuroglioma cell line A172 and H2O2 were employed as an experimental model cell and oxidant. Results: SHCS effectively protected the cells against both the necrotic and apoptotic cell death induced by H2O2. The effect of SHCS was dose-dependent at concentrations ranging from 0.2 to 5mg/ml. SHCS significantly prevented depletion of cellular ATP and activation of poly (ADP-ribose) polymerase induced by H2O2. It also helped mitochondria to preserve its functional integrity estimated by MTT reduction ability. Furthermore, SHCS significantly prevented H202-induced release of cytochrome c into cytosol. Determination of intracellular ROS showed that SHCS might exert its role as a powerful scavenger of intracellular ROS. Conclusions: The present study provides clear evidence for the beneficial effect of SHCS on ROS-induced neuroglial cell injury. The action of SHCS as an ROS-scavenger might underlie the mechanism.

• 대한한의학회지
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• 제24권2호
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• pp.159-165
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• 2003

Objectives : Coptidis rhizoma (CR) is an oriental medicine that has been used in many traditional prescriptions against diabetes mellitus in Korea for centuries. Our purpose was to determine the protective effect and its action mechanism of CR on the cytotoxicity of pancreatic -cell line (RINm5F cell). Methods : In this experiment, we used methods such as MTT assay for detection of cytotoxicity, DNA fragmentation assay for detection of apoptotic cell death, LDH activity assay for detection of necrotic cell death, and measurement of $DiOC_{6}$ (3) retention for detection of mitochondrial membrane potential (MMP). Background : Nitric oxide (NO) is believed to playa key role in the process of pancreatic -cell destruction leading to insulin-dependent diabetes mellitus (IDDM). Results : Exposure of RINm5F cells to chemical NO donor such as S-nitroso-N-acetylpenicillamine (SNAP) induced cytotoxic events such as DNA fragmentation and lactate dehydrogenase (LDH) release into medium. However, pretreatment of RINm5F cells with CR extract ($10~50{\mu\textrm{g}}/ml$) for 3 hours prevented SNAP-induced DNA fragmentation and LDH release into medium through the inhibition of MMP disruption. Conclusions : These results suggest that CR may be a candidate for a therapeutic or preventing agent against IDDM.