• BMB Reports
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• v.38 no.6
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• pp.709-716
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• 2005

Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by $300\;{\mu}M$ W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), “DNA ladders” began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.

• Journal of Life Science
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• v.12 no.2
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• pp.57-60
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• 2002

Apoptosis of vascular smooth muscle cell is observed in the vascular diseases such as atherosclerosis and restenosis. The death of vascular smooth muscle cells can be induced by cytokines and activation of Fas-pathways. It is widely accepted that apoptosis occurs without inflammation. There are, however, reports that apoptosis is not silent. Vascular smooth muscle cells dying by Fas-pathway secreted inflammatory cytokines including monocyte chemoattractant protein-1. This study have investigated whether apoptosis is associated with potent inflammatory cytokine tumor tumor necrosis factor (TNF)-${\alpha}$. The cells which undergo apoptosis by expressing FADD in the absence of tetracycline expressed and secreted TNF-${\alpha}$. When the level of TNF-${\alpha}$ transcript was investigated, dying smooth muscle cells exhibited transcriptional activation of TNF-${\alpha}$. The data indicate that dying vascular smooth muscle cells contribute to inflammation by expressing inflammatory cytokines. The present study suggests that apoptosis could not be silent in certain pathological situations.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.167-175
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• 2014

Chemotherapy has long been considered as one of useful strategies for cancer treatment. It is primarily based on the apoptosis that can selectively kill cancer cells. However, cancer cells can progressively develop an acquired resistance to apoptotic cell death, rendering refractory to chemo- and radiotherapies. Although the mechanism by which cells attained resistance to drug remains to be clarified, it might be caused by either pumping out of them or interfering with apoptotic signal cascades in response to cancer drugs. In case that cancer cells are defective in some part of apoptotic machinery by repeated exposure to anticancer drugs, alternative cell death mechanistically distinct from apoptosis could be adopted to remove cancer cells refractory to apoptosis-inducing agents. This review will mainly deal with harnessing of necrotic cell death, specifically, programmed necrosis and practical uses. Here, we begin with various defects of apoptotic death machinery in cancer cells, and then provide new perspective on programmed necrosis as an alternative anticancer approach.

• Molecules and Cells
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• v.28 no.3
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.1
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• pp.13-23
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• 2005

This study was performed to investigate mistletoe extract-induced apoptosis in oral squamous cell carcinoma. In vivo study, HN22 cells were xenografted in nude mice. After tumor was experimentally induced, mistletoe extract was directly injected on the tumor mass. The specimens were evaluated using light and transmission electron microscopes. In vitro study, HN22 cells were cultured and exposed to mistletoe extract. The cells were evaluated using transmissin electron microscope. To evaluate apoptotic cells, flow cytometric analysis was done. The results were obtained as follows: 1. Light microscopic view of tumor mass showed necrosis at 2-4 weeks. 2. Transmission electron micrographs of tumor mass showed apoptosis and necrosis. 3. In TEM view of cell lines, necrosis and apoptosis were shown with mistletoe extract at $300{\mu}g/ml$, apoptosis was shown with mistletoe extract at $100{\mu}g/ml$. 4. In flow cytometric analysis, early and late apoptosis was shown when using caspase-3Ab and annexin-V, but no significant change was noted when using mebstain and Apo2.7 Ab. In this study, mistletoe extract induced necrosis and apoptosis in the tumor mass was induced by HN22 cells, early and late apoptosis in vitro study. Mistletoe extract was likely to induce cell death in oral squamous cell carcinoma through apoptosis.

• Journal of Life Science
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• v.7 no.1
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• pp.66-72
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• 1997

The term of apoptosis, programmed cell death, was firstly coined to distinguish with necrosis, pathologic cell death, by Kerr in 1972. Although various pathogenic factors are able to occur apoptosis, ti is essential process for normal development and physiology in the animals. Recently in the field of medicine, apoptosis researeh is especially focused in serveral Kind of pathopoiesis problems including cancer, immunodeficiency associated HIV and other virus, autommunity, alzheimer and congenital anormality. The information obtained from the animal model system for apoptosis should be directly applicable to both life science for understanding of development and medicine for practical the rapy. To know the common mechanism of apoptosis, it is prerequisite that the genes and factors responsible for apoptosis should be defined and characterized on the molecular level. The study of apoptosis should contribute largely to biology inculuding cell physiology and development, and both basic and clinical medicine to understand cause of diseases for therapy as well as congenital defect.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.37.1-37.15
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• 2020

Mycobacterium tuberculosis (Mtb) is an etiologic pathogen of human tuberculosis (TB), a serious infectious disease with high morbidity and mortality. In addition, the threat of drug resistance in anti-TB therapy is of global concern. Despite this, it remains urgent to research for understanding the molecular nature of dynamic interactions between host and pathogens during TB infection. While Mtb evasion from phagolysosomal acidification is a well-known virulence mechanism, the molecular events to promote intracellular parasitism remains elusive. To combat intracellular Mtb infection, several defensive processes, including autophagy and apoptosis, are activated. In addition, Mtb-ingested phagocytes trigger inflammation, and undergo necrotic cell death, potentially harmful responses in case of uncontrolled pathological condition. In this review, we focus on Mtb evasion from phagosomal acidification, and Mtb interaction with host autophagy, apoptosis, and necrosis. Elucidation of the molecular dialogue will shed light on Mtb pathogenesis, host defense, and development of new paradigms of therapeutics.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.565-570
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• 1999

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver injury. Due to the detergent-like effect of the hydrophobic bile acids, hepatocellular injury has been attributed to direct membrane damage. However histological findings of cholestatic liver diseases suggest apoptosis can be a mechanism of cell death during cholestatic liver diseases instead of necrosis. To determine the pattern of hepatocellular toxicity induced by bile acid, we incubated primary cultured rat hepatocytes with a hydrophobic bile acid, Glycochenodeoxycholate (GCDC), up to 5 hours. After 5 hours incubation with $400\;{\mu}M$ GCDC, lactate dehydrogenase released significantly. Cell viability, quantitated in propidium iodide stained cells concomitant with fluoresceindiacetate was decreased time- and dose-dependently. Most nuclei with condensed chromatin and shrunk cytoplasm were heavily labelled time- and dose-dependently by a positive TUNEL reaction. These findings suggest that both apoptosis and necrosis are involved in hepatocytes injury caused by GCDC.

• Korean Journal of Veterinary Service
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• v.22 no.3
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• pp.247-255
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• 1999

Sequential morphologic changes in the lymphoid organs were examined after ocular and cloacal inoculation in 3weekold chicks with a highly virulent strain (SH/92) of infectious bursal disease virus (IBDV). The infected chickens were sacrificed at 6, 12, 24, 48, 72, and 96 hrs post inoculation (Pl), and thymus, harderian gland, ceacal tonsil, and spleen were observed. Histologically, the significant lesions were characterized by lymphocyte depletion and the earliest detectable changes were evident at 12 hrs Pl. In thymic cortex, lymphoid depletion with apoptosis and prominent "tingible body macrophages" were observed. As the infection advanced, the lesions showed more severe changes. Dying cells were characterized either by capping of nuclear chromatin (apoptosis) or by cytoplasmic swelling (necrosis). In situ staining for apoptosis, some lymphoid cells revealed typical positive reaction, even the stainability was variable depend on every lymphoid organs. These results suggest that IBBV (SH/92) cause severe damage both primary and secondary lymphoid organs, and both T and B lymphocytes. Also the lymphoid depletion of these organs is caused by necrosis and apoptosis induced by IBDV.d by IBDV.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.5
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• pp.629-636
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• 2019

Objective: The study was designed to determine the cytotoxic effect of gallic acid (GA), obtained by the hydrolysis of tannins, on mice TM4 Sertoli cells apoptosis. Methods: In the present study, non-tumorigenic mice TM4 Sertoli cells were treated with different concentrations of GA for 24 h. After treatment, cell viability was evaluated using WST-1, mitochondrial dysfunction, cells apoptosis and necrosis was detected using JC-1, Hoechst 33342 and propidium iodide staining. The expression levels of Cyclin B1, proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (BAX), and Caspase-3 were also detected by quantitative real-time polymerase chain reaction and Western-blotting. Results: The results showed that 20 to $400{\mu}M$ GA inhibited viability of TM4 Sertoli cells in a dose-dependent manner. Treatment with $400{\mu}M$ GA significantly inhibited PCNA and Cyclin B1 expression, however up-regulated BAX and Caspase-3 expression, caused mitochondrial membrane depolarization, activated Caspase-3, and induced DNA damage, thus, markedly increased the numbers of dead cells. Conclusion: Our findings showed that GA could disrupt mitochondrial function and caused TM4 cells to undergo apoptosis and necrosis.