• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8445-8450
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• 2016

Background: Breast cancer is the most common neoplasm in women and the most frequent cause of death in those between 35 and 55 years of age. All multicellular organisms have an innate immune system, whereas the adaptive or 'acquired' immune system is restricted to vertebrates. This study focused on the effect of conditioned medium isolated from cultured breast cancer cells on NB4 neutrophil-like cells. Materials and Methods: In the current study neutrophil-like NB4 cells were incubated with MCF-7 cell-conditioned medium. After 6 h incubation the intracellular receptor TLR2, was analyzed. Results: The results revealed that MCF-7 cell-conditioned medium elicited expression of TLR2 in NB4 cells. Conclusions: This treatment would result in the production of particular stimulants (i.e. soluble cytokines), eliciting the expression of immune system receptors. Furthermore, the flow cytometry results demonstrated that MCF-7 cell-conditioned medium elicited an effect on TLR2 intracellular receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.73-78
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• 2014

Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-${\kappa}B$) translocation.

• Molecules and Cells
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• 제37권4호
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• pp.345-355
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• 2014

Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

• 생명과학회지
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• 제21권11호
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• pp.1641-1651
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• 2011

TNF ligand 군에 속하는 Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L)은 death receptor를 통한 세포사멸을 유도하는 것으로 알려졌다. TRAIL은 정상세포에서는 세포사를 일으키지 않고 암세포에서만 특이적으로 세포사멸을 유도함으로써 잠재력 있는 항암제로 주목을 받고 있다. 그러나, 최근 연구에 의하면 악성 신장암과 간암과 같은 일부 암에서는 TRAIL에 의한 세포사에 저항성을 가지는 것으로 알려져 있다. 그러므로, TRAIL 만으로는 다양한 악성종양을 위한 치료법으로 적절하지 않다. TRAIL에 대한 저항성을 가지는 분자적 기전을 이해하고, TRAIL 저항성을 극복할 수 있는 증감제를 밝혀내는 것이 보다 효율적인 TRAIL을 이용한 암세포 치료 전략에 필요하다. 화학치료제들이 TRAIL 수용체인 death receptor의 발현을 증가시키고, 세포 내의 TRAIL에 의한 신호전달 체계를 활성화 시키는 것으로 알려져 있고, 이러한 기전을 통하여 다양한 화학치료제들이 TRAIL에 의한 세포사멸을 증가시키는 것을 확인하였다. 이 논문에서, 우리는 TRAIL에 의한 세포 사멸을 증가시키기 위한 생물학적 약물을 정리하고, 그 분자적 기전을 고찰한다.

• 약학회지
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• 제56권1호
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• pp.35-41
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• 2012

In this study, we examined the effect of luteolin to enhance TRAIL-induced anticancer effect in SK-Hep1 cells. We found that combined use of TRAIL with luteolin markedly enhanced the cytotoxicity compared to either agent alone by inducing apoptosis. Furthermore, combined treatment of TRAIL with luteolin significantly induced activation of death receptor pathway-related proteins as well as PARP-cleavage and activation of effector caspases. Also, our result indicated that upregulation of DR4 and DR5 by luteolin combination may contribute to enhanced susceptibility of SK-Hep1 cells to TRAIL.

• 한국동물위생학회지
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• 제39권2호
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• pp.131-136
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• 2016

Clostridium novyi (C. novyi) is a gram positive, non-capsulated, motile, obligatory anaerobe that produces endospores. Both C. novyi type A and B produce a bacteriophage encoded lethal alpha toxin which belongs to a family of large clostridial cytotoxins. These large clostridial cytotoxins of C. novyi bind to the uncharacterized receptors on host vascular endothelial cells, which leads to the loss of integrity of the vascular endothelium with subsequent edema, refractory hypotension, organ failure, and sudden death. A total of 13 sudden death cases were submitted to Chonbuk National University-Veterinary Diagnostic Center between June and October, 2015. The samples, mainly liver, were collected in sterile vials after necropsy and processed within 12~24 hours for diagnosis, isolation and identification of C. novyi. All of the 4 gram positive samples showed amplification by PCR. Out of 4 positive samples, 3 were detected to be C. novyi type B and 1 was detected as C. novyi type A. Based on the 16S rDNA sequence analysis, 1 case (150564) showed 99% similarity with C. novyi type A while other 3 cases (150388, 150557 and 150775) presented 99% similarity with C. novyi type B. Based on the results, C. novyi was found to be prevalent in Korean pig farms and causes sudden death to finishing pigs or sows during summer season. Thus, C. novyi should be considered for differential diagnosis on sudden death cases during the summer season.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2009년도 추계학술대회
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• pp.190-192
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• 2009

Kainic acid (KA), an agonist for kainate and AMPA receptors, is an excitatory neurotoxic substance. Vitamin E such as alpha-tocopherol and alpha-tocotrienol is a chain-breaking antioxidant, preventing the chain propagation step during lipid peroxidation. In the present study, we have investigated the neuroprotective effects of alphatocopherol and alpha-tocotrienol on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC). After 15h KA treatment, delayed neuronal death was detected in CA3 region. Alpha-tocopherol and alpha-tocotrienol increased cell survival and reduced the number of TUNEL-positive cells in CA3 region. These data suggest that alpha-tocopherol and alpha-tocotrienol treatment have protective effects on KA-induced cell death

• BMB Reports
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• 제35권1호
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• pp.7-18
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• 2002

The major function of the thymus is to eliminate developing thymocytes that are potentially useless or autoreactive, and select only those that bear functional T cell antigen receptors (TCRs) through fastidious screening. It is believed that glucocorticoids (GCs) are at least in part responsible for cell death during death by neglect. In this review, we will mainly cover the topic of the GC-induced apoptosis of developing thymocytes. We will also discuss how thymocytes that are fated to die by GCs can be rescued from GC-induced apoptosis in. response to a variety of signals with antagonizing properties for GC receptor (GR) signaling. Currently, a lot of evidence supports the notion that the decision is made as a result of the integration of the multiple signal transduction networks that are triggered by GR, TCR, and Notch. A few candidate molecules at the converging point of these multiple signaling pathyways will be discussed. We will particularly describe the role of the SRG3 protein as a potent modulator of GC-induced apoptosis in the crosstalk.

• BMB Reports
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• 제39권5호
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• pp.556-559
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• 2006

The Bcl-2 family of proteins regulates mitochondrial functions during cell death by modulating the efflux of death-promoting proteins such as cytochrome c and endonuclease G. Upon the binding of death ligands to their receptors, caspase-8 cleaves Bid, a BH3-only protein, into tBid that causes the mitochondrial damages resulting in the release of cytochrome c and endonuclease G. Also, another BH3-only protein, hNoxa, has been shown to induce the efflux of cytochrome c from the mitochondria. Whether the efflux proteins from the mitochondria in response to tBid or hNoxa are the same or different, however, has not been addressed. We have demonstrated that endonuclease G activities are not detectable among the proteins released from isolated mitochondria by hNoxa but are detectable in that by tBid. These results suggest that the efflux of proteins from the mitochondria are differentially modulated by tBid and hNoxa.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.59-67
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• 2023

Thrombin is a serine protease that participates in a variety of biological signaling through protease-activated receptors. Intestinal myofibroblasts play central roles in maintaining intestinal homeostasis. In this study, we found that thrombin-induced apoptosis is mediated by the calcium-mediated activation of cytosolic phospholipase A₂ in the CCD-18Co cell. Thrombin reduced cell viability by inducing apoptosis and proteinase-activated receptor-1 antagonist attenuated thrombin-induced cell death. Endogenous ceramide did not affect the cell viability itself, but a ceramide-mediated pathway was involved in thrombin-induced cell death. Thrombin increased intracellular calcium levels and cytosolic phospholipase A₂ activity. The ceramide synthase inhibitor Fumonisin B1, intracellular calcium chelator BAPTA-AM, and cytosolic phospholipase A₂ inhibitor AACOCF₃ inhibited thrombin-induced cell death. Thrombin stimulated arachidonic acid release and reactive oxygen species generation, which was blocked by AACOCF₃, BAPTA-AM, and the antioxidant reagent Trolox. Taken together, thrombin triggered apoptosis through calcium-mediated activation of cytosolic phospholipase A₂ in intestinal myofibroblasts.