• Molecules and Cells
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• 제39권4호
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• pp.358-366
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• 2016

The digestive system is gaining interest as a major regulator of various functions including immune defense, nutrient accumulation, and regulation of feeding behavior, aside from its conventional function as a digestive organ. The Drosophila midgut epithelium is completely renewed every 1-2 weeks due to differentiation of pluripotent intestinal stem cells in the midgut. Intestinal stem cells constantly divide and differentiate into enterocytes that secrete digestive enzymes and absorb nutrients, or enteroendocrine cells that secrete regulatory peptides. Regulatory peptides have important roles in development and metabolism, but study has mainly focused on expression and functions in the nervous system, and not much is known about the roles in endocrine functions of enteroendocrine cells. We systemically examined the expression of 45 regulatory peptide genes in the Drosophila midgut, and verified that at least 10 genes are expressed in the midgut enteroendocrine cells through RT-PCR, in situ hybridization, antisera, and 25 regulatory peptide-GAL transgenes. The Drosophila midgut is highly compartmentalized, and individual peptides in enteroendocrine cells were observed to express in specific regions of the midgut. We also confirmed that some peptides expressed in the same region of the midgut are expressed in mutually exclusive enteroendocrine cells. These results indicate that the midgut enteroendocrine cells are functionally differentiated into different subgroups. Through this study, we have established a basis to study regulatory peptide functions in enteroendocrine cells as well as the complex organization of enteroendocrine cells in the Drosophila midgut.

• 한국군사과학기술학회지
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• 제20권4호
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• pp.543-550
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• 2017

Various chemical properties including density and heat of formation of 1-substitued trinitroimidazoles (TNIs) were estimated by using density functional theory (DFT). Using chemical properties estimated by DFT, explosive performance and sensitivity of 1-substitued TNIs were analyzed by following the ADD Method-1 procedure. The results were displayed on two-dimensional performance-sensitivity plot, and were compared with those of explosive molecules commonly used in many military systems. Different 1-substituents of TNI made that both explosive performance and impact sensitivity were changed significantly. Methyl substituted TNI became moderately insensitive and slightly less powerful. Amino, fluoro, picryl, and difluoroamino substituted TNIs were highly powerful like RDX and HMX, but greatly sensitive. Nitro substituted TNI was predicted to be extremely sensitive to be handled as a secondary explosive.

• The Plant Pathology Journal
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• 제17권2호
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• pp.88-93
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• 2001

Oxidative stress is one of the major limiting factor in plant productivity. Reactive oxygens species (ROS) generated during metabolic processes damage cellular functions and consequently lead to disease, senescence and cell death. Plants have evolved an efficient defense system by which the ROS is scavenged by antioxidant enzymes such as superoxide dismutase (SOD) and ascorbate peroxidase (APX). Attempts to reduce oxidative damages under the stress conditions have included the manipulation of 갠 scavenging enzymes by gene transfer technology. Increased SOD activities of transgenic plants lead to increased resistance against oxidative stresses derived from methyl viologen (MV), and from photooxidative damage caused by high light and low temperature. Transgenic tobacco plants overexpressing APX showed reduced damage following either MV treatment of photooxidative treatment. Overexpression of glutathion reductase (GR) leads to increase in pool of ascorbate and GSH, known as small antioxidant molecules. These results indicate through overexpression of enzymes involved in ROS-scavenging could maintain or improve the plant productivities under environment stress condition. In this study, the rational approaches to develop stress-tolerant plants by gene manipulation of antioxidant enzymes will be introduced to provide solutions for the global food and environmental problems in the $21^\textrm{st}$ century.

• The Plant Pathology Journal
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• 제27권1호
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• pp.53-58
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• 2011

Systemic acquired resistance is a form of inducible resistance that is triggered in systemic healthy tissues of local-infected plants. Several candidate signaling molecules emerged in the past two years, including the methylated derivatives of well-known defense hormones salicylic acid (SA) and jasmonic acid (JA). In our present study, the symptom on Cucumber mosaic virus (CMV) infected Arabidopsis leaves in 0.1 mM SA or 0.06 mM JA pre-treated plants was lighter (less reactive oxygen species accumulation and less oxidative damages) than that of the control group. JA followed by SA (JA${\rightarrow}$SA) had the highest inhibitory efficiency to CMV replication, higher than JA and SA simultaneous co-pretreatment (JA+SA), and higher than a JA or a SA single pretreatment. The crosstalk between the two hormones was further investigated at the transcriptional levels of pathogenesis-related genes. The time-course measurement showed JA might play a more important role in the interaction between JA and SA.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.346-351
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• 2012

Cells show various stress signs when they are challenged with severe physiological problems. Majority of such cellular stresses are conveyed to endoplasmic reticulum (ER) and unfolded protein response (UPR) serves as typical defense mechanism against ER stress. This study investigated an interaction between ER stress agents using macropage cell line Raw 264.7. When activated by lipopolysaccharide (LPS), the cell lines showed typical indicators of ER stress. Along with molecular chaperones, the activation process leads to the production of additional inflammatory mediators. Following activation, the macrophage cell line was further treated with TUN and characterized in terms of chaperone expression and cytokine secretion. When treated with TUN, the activated macrophage cell leads to increased secretion of IL-6 although expression of ER stress markers, GRP94 and GRP78 increased. The secretion of cytokines continued until the addition of BFA which inhibits protein targeting from ER to Golgi. However, secretion of cytokines was ceased upon dual treatments with BFA and TG. This result strongly implies that cells may differently deal with various polypeptides depending on the urgency in cellular function under ER stress. Considering IL-6 is one of the most important signal molecules in macrophage, the molecule might be able to circumvent ER stress and UPR to reach its targeting site.

• Molecules and Cells
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• 제21권1호
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• pp.21-28
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• 2006

The interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase PKR plays a key role in interferon-mediated host defense against viral infection, and is implicated in cellular transformation and apoptosis. We have isolated a cDNA of simian PKR encoding a product with 83% amino acid identity to the human homolog and showed that PKR expression is significantly attenuated in the Vero E6 African green monkey kidney cells devoid of type I interferon genes. A variant form of PKR lacking the exon 12 in the kinase domain is produced in these cells, presumably from an alternatively spliced transcript. Unlike wild type PKR, the variant protein named PKR-${\Delta}E12$ is incapable of auto-phosphorylation and phosphorylation of eIF2-${\alpha}$, indicating that the kinase sub-domains III and IV embedded in exon 12 are indispensable for catalytic function. PKR-${\Delta}E12$ had no dominant negative effect but was weakly phosphorylated in trans by wild type PKR.

• Molecules and Cells
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• 제26권4호
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• pp.323-328
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• 2008

Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to maladaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficult-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell lifespan determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anti-cancer therapies.

• Molecules and Cells
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• 제44권9호
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• pp.670-679
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• 2021

Vesicle-associated membrane proteins 721 and 722 (VAMP721/722) are secretory vesicle-localized arginine-conserved soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) to drive exocytosis in plants. They are involved in diverse physiological processes in plants by interacting with distinct plasma membrane (PM) syntaxins. Here, we show that synaptotagmin 5 (SYT5) is involved in plant defense against Pseudomonas syringae pv tomato (Pst) DC3000 by regulating SYP132-VAMP721/722 interactions. Calcium-dependent stimulation of in vitro SYP132-VAMP722 interaction by SYT5 and reduced in vivo SYP132-VAMP721/722 interaction in syt5 plants suggest that SYT5 regulates the interaction between SYP132 and VAMP721/722. We interestingly found that disease resistance to Pst DC3000 bacterium but not to Erysiphe pisi fungus is compromised in syt5 plants. Since SYP132 plays an immune function to bacteria, elevated growth of surface-inoculated Pst DC3000 in VAMP721/722-deficient plants suggests that SYT5 contributes to plant immunity to Pst DC3000 by promoting the SYP132-VAMP721/722 immune secretory pathway.

• Molecules and Cells
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• 제44권5호
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• pp.342-355
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• 2021

The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

• Molecules and Cells
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• 제44권6호
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• pp.408-421
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• 2021

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.