• Oncology Letters
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• 제18권6호
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• pp.5889-5896
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• 2019

The elimination of residual microscopic cancer cells is important cancer treatment. The immunoediting theory describes the balance between the immune system and cancer cells. The current study investigated changes in the immune system during the elimination of cancer cells and evaluated the influence of cluster of differentiation (CD)4 or CD8 depletion. A human squamous cell cancer cell line (SNU1041) was injected in the lateral tongue of immunocompetent mice and the changes in the CD4, CD8, CD11b, CD19, CD40 and CD40 ligand (L) populations in the blood, lymph nodes and spleen were evaluated using flow cytometry, and changes in serum cytokine levels were evaluated using a magnetic bead panel. Cancer cell elimination was delayed by CD4 depletion but not by CD8 depletion. The CD8-depleted group indicated increased levels of CD40L, interferon-gamma, interleukin (IL)-10, IL-6, and tumor necrosis factor-α. It was concluded that CD4 served a crucial role in the elimination of human cancer cells. Furthermore, the efficacies of CD40 agonist and programmed cell death protein 1 (PD1) antagonist treatments were assessed in CD4-depleted mice. CD40 agonist treatment resulted in faster cancer cell elimination and increased cytokine excretion. In conclusion, CD4 or CD40L significantly influenced cancer elimination. CD40 agonist antibodies may be potent adjuvant agents that can be used in patients with reduced CD4 or CD40L expression

• The Plant Pathology Journal
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• 제39권6호
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• pp.584-591
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• 2023

Active plant immune response involving programmed cell death called the hypersensitive response (HR) is elicited by microbial effectors delivered through the type III secretion system (T3SS). The marine bacterium Hahella chejuensis contains two T3SSs that are similar to those of animal pathogens, but it was able to elicit HR-like cell death in the land plant Nicotiana benthamiana. The cell death was comparable with the transcriptional patterns of H. chejuensis T3SS-1 genes, was mediated by SGT1, a general regulator of plant resistance, and was suppressed by AvrPto1, a type III-secreted effector of a plant pathogen that inhibits HR. Thus, type III-secreted effectors of a marine bacterium are capable of inducing the nonhost HR in a land plant it has never encountered before. This suggests that plants may have evolved to cope with a potential threat posed by alien pathogen effectors. Our work documents an exceptional case of nonhost HR and provides an expanded perspective for studying plant nonhost resistance.

• 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.

• 생명과학회지
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• 제7권1호
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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.

• KSBB Journal
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• 제28권4호
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• pp.260-268
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• 2013

Transgenic plant cell cultures are an attractive expression system for the production of industrial and pharmaceutical proteins because of their advantages in safety and low production cost. Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) was produced and secreted when sugar was depleted in culture medium by transgenic rice cell lines (Oryza sativa L.) using RAmy3D promoter. Due to the production of the target protein by sugar depletion, concomitant occurrence of cell death is inevitable. For that reason, inhibition of cell death for enhancing productivity was necessary for the production period without energy sources. Supplementation of 0.1 mM sodium nitroprusside improved cell viability by 1.4-fold and maximum hCTLA4Ig production by 1.3-fold compared to those of control. Addition of 1 and 10 mM glutathione, N-acetylcysteine (NAC), and nicotinamide inhibited apoptotic-like programmed cell death by decreasing the activity of reactive oxygen species. Production hCTLA4Ig was enhanced 1.4-, 1.25-, and 1.15-fold with 10 mM NAC, 1 mM NAC, and 1 mM glutathione, respectively. In addition, it was found that the supplementation of NAC enhanced the cell viability.

• 동의신경정신과학회지
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• 제11권1호
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• pp.37-46
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• 2000

We investigated the effects of lemon pure essential oils on the heat shock-induced apoptosis in human astrocyte cell line CCF-STTG1. In previous studies, hear shock has been reported to induce the apoptosis or programmed cell death through the activation of caspase-3. Treatment of CCF-STTG1 cells with heat shock markedly induced apoptotic cell death as determined by flow cytometry. Interestingly, pretreatment of CCF-STTG1 cells with lemon pure essential oils inhibited the heat shock-induced apoptosis. Lemon also inhibited the heat shock-induced apoptosis in primary cultured rat astrocytes. To determine whether lemon inhibits the heat shock-induced activation of these apoptotic proteases, activation of CPP32 was assessed by Western blotting. Consistent with flow cytometry, DNA fragmentation and giemsa staining, heat shock-induced activation of CPP32 was blocked by lemon pure essential oil. PARP, cysteine protease substrates were fragmented as a consequence of apoptosis by heat shock. Lemon oil inhibited the PARP fragmentation. This essential oil also inhibited the heat shock-induced activation of caspase-3. These results suggest that lemon pure essential oils may modulate the apoptosis through the activation of the ICE-like caspases.

• 동의신경정신과학회지
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• 제11권2호
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• pp.1-9
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• 2000

In previous studies, heat shock has been reported to induce the apoptosis or programmed cell death through the activation of caspase-3. 1 investigated the effect of juniper pure essential oil on the heat shock-induced apoptosis in human astrocyte cell line CCF-STTGI. Treatment of the astrocytes with heat shock markedly induced apoptotic cell death. However, pretreatment of the astrocytes with juniper oil ingibited the heat shock-induced apoptosis. To determine whether juniper inhibits the heat shock-induced activation of these apoptotic proteases, activation of CPP32 was assessed by Western blotting. Consistent with flow cytometry. DNA fragmentation and giemsa staining, heat shock-induced activation of CPP32 was blocked by juniper oil. Poly(ADP-ribose) polymerase (PARP), cysteine protease substrates were fragmented as a consequence of apoptosis by heat shock. Juniper oil inhibited the PARP fragmentation. This juniper oil also inhibited the heat shock-induced activation of caspase-3. These results suggest that juniper oil may modulate the apoptosis through the activation of the interleukin-1-converting enzyme-like protease.

• IMMUNE NETWORK
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• 제16권2호
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• pp.134-139
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• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• Parasites, Hosts and Diseases
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• 제49권1호
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• pp.17-23
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• 2011

The aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on Leishmania major (MRHO/IR/75/ER) and L. tropica (MHOM/IR/02/Mash10) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. major and L. tropica viability and the obtained results were expressed as 50% inhibitory concentration (IC50). Also, 50% effective doses (ED50) for L. major and L. tropica amastigotes were also determined, Annexin-V FLUOS staining was performed to study the cell death properties of miltefosine using FAGS analysis. Qualitative analysis of the total genomic DNA fragmentation was performed by agarose gel electrophoresis. Furthermore, to observe changes in cell morphology, promastigotes were examined using light microscopy. In both strains of L. major and L. tropica, miltefosine induced dose-dependent death with features of apoptosis, including cell shrinkage, DNA laddering, and externalization of phosphatidylserine. The IC50 was achieved at 22 ${\mu}M$ and 11 ${\mu}M$ for L. major and L. tropica after 48 hr of incubation, respectively. ED50 of L. major and L. tropica amastigotes were 5.7 ${\mu}M$ and 4.2 ${\mu}M$, respectively. Our results indicate that miltefosine induces apoptosis of the causative agent of cutaneous leishmaniasis in a dose-dependent manner. Interestingly, L. major did not display any apoptotic changes when it was exposed to miltefosine in concentrations sufficient to kill L. tropica.

• Animal cells and systems
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• 제7권1호
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• pp.1-9
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• 2003

Programmed cell death, or apoptosis, is one of the most studied areas of modern biology. Apoptosis is a genetically regulated process, which plays an essential role in the development and homeostasis of higher organisms. Mitochondria, known to play a central role in regulating cellular metabolism, was found to be critical for regulating apoptosis induced under both physiological and pathological conditions. Mitochondria are a major source of reactive oxygen species (ROS) but they can also serve as its target during the apoptosis process. Release of apoptogenic factors from mitochondria, the best known of which is cytochrome c, leads to assembly of a large apoptosis-inducing complex called the apoptosome. Cysteine pretenses (called caspases) are recruited to this complex and, following their activation by proteolytic cleavage, activate other caspases, which in turn target for specific cleavage a large number of cellular proteins. The redox regulation of apoptosis during and after cytochrome c release is an area of intense investigation. This review summarizes what is known about the biological role of ROS and its targets in apoptosis with an emphasis on its intricate connections to mitochondria and the basic components of cell death.