• Biomedical Science Letters
• /
• v.28 no.3
• /
• pp.192-194
• /
• 2022

The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

• Fisheries and Aquatic Sciences
• /
• v.5 no.1
• /
• pp.32-35
• /
• 2002

In this study, we investigated the mechanism of cell death in rhabdovirus-infected cells, chinook salmon embryonic cell line (CHSE-2l4) infected with hirame rhabdovirus (HIRRV). Studies using light microscopy, fluorescence microscopy, TUNEL method, electron microscopy, and agarose gel electrophoresis revealed changes in the cell morphology and DNA fragmentation indicative of apoptosis in early infection. It was observed that HIRRV induced apoptosis as well as necrosis in infected cells.

• BMB Reports
• /
• v.35 no.1
• /
• pp.67-86
• /
• 2002

Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of $Ca^{2+}$ and $Na^+$ that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.138-143
• /
• 2023

Liver fibrosis is caused by metabolic problems such as cholestasis, genetic problems, or viral infections. Inhibiting hepatic stellate cell (HSC) activation or inducing selective apoptosis of activated HSCs is used as a treatment strategy for liver fibrosis. It has been reported that when HSCs are activated, their apoptosis sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is enhanced because the expression of death receptor 5 is elevated. Finding a natural compound that can enhance the apoptotic effect of TRAIL on HSCs is a necessary strategy for liver fibrosis treatment. It was confirmed here that mangosteen-derived gartanin increased the effect of TRAIL-induced apoptosis by increasing the expression of DR5 in a p38-dependent manner in the hepatic stellate cell line LX-2. Combined treatment with gartanin and TRAIL accelerated DNA cleavage through caspase-3 activation and enhanced antifibrotic effects in LX-2 cells.

• Korean Journal of Veterinary Pathology
• /
• v.3 no.1
• /
• pp.27-33
• /
• 1999

Phosphamidon(PMD) is orgnophosphate insecticide broadly using in agriculture. In order to study PMD toxicity in the testis, histopathological change and apoptosis were assessed following acute and chronic oral administration in rats and chickens. In acute studies, histopathological changes included necrosis and desquamation of spermatogenic cells, multinucleated giant cells in the lumen of seminiferous tubules, and necrotic cells and the giant cells in the epididymal lumen. Atrophy of seminiferous tubule was seen in the chronic exposure with low doses. The toxic effects of PMD in chronic exposure including clinical signs and histopathological changes were more pronounced in chickens than rats. Apoptosis assessment was performed by TUNEL method and Hoechst staining. TUNEL-positive apoptotic cells were found in spermatocytes of seminiferous tubules, testicular apoptosis was more prominent following acute exposure than control and chronic exposure. Above mentioned result noticed that PMD causes apoptotic death and effects directly the spermatocytogenesis.

• Molecules and Cells
• /
• v.22 no.1
• /
• pp.21-29
• /
• 2006

The aim of this study was to determine if hydrogen peroxide ($H_2O_2$) generated by glucose oxidase (GO) induces apoptosis or necrosis of BJAB cells and which radical is the direct mediator of cell death. We found that GO produced $H_2O_2$ continuously in low concentrations, similar to in vivo conditions, and decreased proliferation and cell viability in a dose-dependent manner. The GO-mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the cells after H33342/Annexin V/propidium iodide staining. Decreases of mitochondrial membrane potential and intracellular glutathione level were found to be critical events in the $H_2O_2$-mediated apoptosis. Additional experiments revealed that $H_2O_2$ exerted its apoptotic action through the formation of hydroxyl radicals via the Fenton rather than the Haber-Weiss reaction. Moreover, intracellular redox-active iron, but not copper, participated in the $H_2O_2$-mediated apoptosis.

• YAKHAK HOEJI
• /
• v.55 no.1
• /
• pp.49-55
• /
• 2011

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is one of the promising anti-cancer agent because of its ability to selectively induce apoptosis in tumor cell lines but not in normal cells. However, TRAIL resistance has been reported in some cancer cells including hepatocarcinoma cells. Therefore, studies of agents that sensitize TRAIL-resistant cancer cells could be a effective therapeutic approach in cancer management. In our study, we examined the effect of combination of TRAIL with apigenin in human hepatocellular carcinoma cells. As a result, the combined use of TRAIL and apigenin significantly enhanced the cytotoxicity in PLC-PRF5 cells. Flow cytometry analysis after annexin V-FITC/PI dual staining showed that this increase of cell cytotoxicity was related to enhanced apoptosis in combined treatment of TRAIL with apigenin. Furthermore, synergistic induction of apoptosis was also confirmed by observation of morphological changes and annexin V-FITC/PI fluorescence. Our findings suggests that apigenin has the potential to improve the efficiency of TRAIL-based therapies in human hepatocellular carcinoma cells. Further study is needed to reveal the molecular mechanisms of this combined therapy.

• Journal of Acupuncture Research
• /
• v.30 no.1
• /
• pp.43-55
• /
• 2013

I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.

• Restorative Dentistry and Endodontics
• /
• v.24 no.1
• /
• pp.187-199
• /
• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.21 no.3
• /
• pp.18-33
• /
• 2008

Purpose: The research is to investigate the effect of TFE on apoptosis of human-derived breast cancer cells, to find out the relationship with apoptosis. Methods: Human-derived breast adenocarcinoma cell line, MCF-7 cells were treated by TFE with various concentration. The inducement effect of TFE on cell apoptosis was observed with MTT assay and the relationship between the treatment and apoptosis was investigated with FACS analysis, TUNEL assay and DNA laddering assay and the change in the protein levels of PARP and caspase-3 activities were also observed. The release of cytochrome-c was observed to find out the pathway of apoptosis induced by TFE. Results: The cell apoptosis was significantly induced in MCF-7 cells treated with TFE in concentration-dependent and time-dependent manner. It was verified by FACS analysis, TUNEL assay, DNA laddering assay that cell-death was caused not by necrosis but by apoptosis. The activity of PARP and caspase were increased concentration-dependently. The release of cytocrome-c was decreased in proportion to the concentration of the fruit extract. It therefore demonstrated that mitochondria were involved in apoptosis induced by TFE. The appearance of Bcl-2 protein was decreased concentration-dependently. Conclusion: The treatment by TFE induced apoptosis of human breast adenocarcinoma cell line, MCF-7. It seems likely that cell-death was caused by apoptosis and mitochondria were involved in it. The mechanism of protein change causing apoptosis seems related to the inhibition of Bcl-2 protein, the promotion of inversion from cytochrome-c into cytosol, the activation of caspase and the promotion of PARP cleavage.