• Molecules and Cells
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• v.21 no.2
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• pp.229-236
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• 2006

Gaegurin 4 (GGN4), a novel peptide isolated from the skin of a Korean frog, Rana rugosa, has broad spectrum antimicrobial activity. A number of amphipathic peptides closely related to GGN4 undergo a coil to helix transition with concomitant oligomerization in lipid membranes or membrane-mimicking environments. Despite intensive study of their secondary structures, the oligomeric states of the peptides before and after the transition are not well understood. To clarify the structural basis of its antibiotic action, we used analytical ultracentrifugation to define the aggregation state of GGN4 in water, ethyl alcohol, and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The maximum size of GGN4 in 15% HFIP corresponded to a decamer, whereas it was monomeric in buffer. The oligomeric transition is accompanied by a cooperative 9 nm blue-shift of maximum fluorescence emission and a large secondary structure change from an almost random coil to an ${\alpha}$-helical structure. GGN4 induces pores in lipid membranes and, using electrophysiological methods, we estimated the diameter of the pores to be exceed $7.3{\AA}$, which suggests that the minimal oligomer structure responsible is a pentamer.

• Molecules and Cells
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• v.37 no.11
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• Molecules and Cells
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• v.27 no.6
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• pp.621-627
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• 2009

Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 is associated with an elongated polyglutamine tract in ataxin-1, the SCA1 gene product. As summarized in this review, recent studies have clarified the molecular mechanisms of SCA1 pathogenesis and provided direction for future therapeutic approaches. The nucleus is the subcellular site where misfolded mutant ataxin-1 acts to cause SCA1 disease in the cerebellum. The role of these nuclear aggregates is the subject of intensive study. Additional proteins have been identified, whose conformational alterations occurring through interactions with the polyglutamine tract itself or non-polyglutamine regions in ataxin-1 are the cause of SCA-1 cytotoxicity. Therapeutic hope comes from the observations concerning the reduction of nuclear aggregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.116-117
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• 2006

Increasing the solvent molecular size leads to shrinkage of the polymer chains and increase of the critical overlap concentrations. In addition, the dependency of $R_{g}$ on polymer concentration under normal solvent conditions and solvent molecular size is in good agreement with scaling laws. When the solvent molecular size approaches the ideal end-to-end distance of the polymer chain, an extra aggregation of polymer chains occurs, and the solvent becomes the so-called medium-sized solvent. When the size of solvent molecules is smaller than the medium size, the polymer chains are swollen or partially swollen. However, when the size of solvent molecules is larger than the medium size, the polymer coils shrink and segregate, enwrapped by the large solvent molecules.

• BMB Reports
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• v.29 no.1
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• pp.68-72
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• 1996

Ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), secondary bile acids, have been shown to have a cell differentiation activity in mouse F9 teratocarcinoma stem cells. Treatment with bile acids induced morphological changes, including cytoplasmic and nuclear membrane blebbing, aggregation of organelles, and chromatin condensation, corresponding to apoptosis. Moreover, the bile acids induced intemucleosomal DNA fragmentation, a hallmark of apoptosis. In addition, the expression of c-jun was increased, but that of c-myc and laminin was decreased during apoptosis induced by the bile acids in F9 cells. These results suggest that the bile acids can induce apoptosis in F9 cells. Furthermore, the c-jun expression may be related to the apoptosis induced by UDCA or LCA in F9 cells.

• The Plant Pathology Journal
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• v.31 no.4
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• pp.323-333
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• 2015

As sessile organisms, plants are exposed to persistently changing stresses and have to be able to interpret and respond to them. The stresses, drought, salinity, chemicals, cold and hot temperatures, and various pathogen attacks have interconnected effects on plants, resulting in the disruption of protein homeostasis. Maintenance of proteins in their functional native conformations and preventing aggregation of non-native proteins are important for cell survival under stress. Heat shock proteins (HSPs) functioning as molecular chaperones are the key components responsible for protein folding, assembly, translocation, and degradation under stress conditions and in many normal cellular processes. Plants respond to pathogen invasion using two different innate immune responses mediated by pattern recognition receptors (PRRs) or resistance (R) proteins. HSPs play an indispensable role as molecular chaperones in the quality control of plasma membrane-resident PRRs and intracellular R proteins against potential invaders. Here, we specifically discuss the functional involvement of cytosolic and endoplasmic reticulum (ER) HSPs/chaperones in plant immunity to obtain an integrated understanding of the immune responses in plant cells.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.279-285
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• 2015

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1628-1634
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• 2009

Small heat shock proteins (sHSPs) function as molecular chaperones that protect cells against environmental stresses. In the present study, the genes of hsp17.6 and hsp17.7, cytosolic class I sHSPs, were cloned from a tropical plant, Ageratina adenophorum. Their C-terminal domains were highly conserved with those of sHSPs from other plants, indicating the importance of the C-terminal domains for the structure and activity of sHSPs. The recombinant HSP17.6 and HSP17.7 were applied to determine their chaperone function. In vitro, HSP17.6 and HSP17.7 actively participated in the refolding of the model substrate citrate synthase (CS) and effectively prevented the thermal aggregation of CS at $45^{\circ}C$ and the irreversible inactivation of CS at $38^{\circ}C$ at stoichiometric levels. The prior presence of HSP17.7 was assumed to suppress the thermal aggregation of the model substrate CS. Therefore, this report confirms the chaperone activity of HSP17.6 and HSP17.7 and their potential as a protectant for active proteins.

• Polymer(Korea)
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• v.30 no.6
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• pp.556-562
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• 2006

Quarternized poly(4-vinyl pyridine)s have been prepared by the reaction of poly (4-vinyl pyridine)s (Mw=50 kg/mol and 200 kg/mol) and alkylating agents varying the carbon numbers of the alkyl groups (m):dimethyl sulfate (m=1) as well as bromoalkane (m= 5, 8, 12, 16, and 22) was used as an alkylating agent. The degree of alkylation was determined by using an elemental analysis and NMR spectroscopy. As a result, polyelectrolytes were obtained by the almost full alkylation of poly (4-vinyl pyridine)s. The critical aggregation concentration (CAC) was determined by measuring the change of turbidity occurred by addition of sodium dodecyl sulfate (SDS) into aqueous solution of quarternized poly-(4-vinyl pyridine)s, and the dependence of molecular weight of polymer, the length of N-alkyl group and concentration of NaCl upon CAC was investigated. As a result, as the molecular weight or the length of alkyl group was increased, less amount of SDS Gould induce the aggregation.

• Journal of Integrative Natural Science
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• v.13 no.4
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.