• 동의신경정신과학회지
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• 제12권2호
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• 대한한의학회지
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• 제29권3호
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• pp.76-87
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• 2008

Objectives: In this study, the author investigated whether Haengso-tang (HST) and Chwiyeon-tang (CHT) affect both in vitro mucin secretion and MUC5AC gene expression in airway epithelial cells and in vivo mucin secretion from animal model for airway mucus hypersecretion. Materials and Methods: Confluent HTSE cells (non-labeled) were chased for 30 min in the presence of HST and CHT to assess the effects of the agents on mucin secretion by enzyme-linked immunosorbent assay (ELISA), with removal of oriental herbal medicine extract from each agent-treated sample by centrifuge microfilter. Also, the effects of the agents on TNF- or EGF-induced MUC5AC gene expression in human airway epithelial cells (NCI-H292) were investigated. The author also induced hypersecretion of airway mucus by exposure of rats to SO2 for 3 weeks. Effects of orally-administered HST and CHT during 1 week on in vivo mucin secretion from tracheal goblet cells of rats were assessed using ELISA. Results: (1) HST significantly decreased in vitro mucin secretion from cultured HTSE cells. However, CHT did not affect in vitro mucin secretion from HTSE cells; (2) CHT significantly inhibited the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells. However, HST did not affect the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells; (3) CHT significantly inhibited hypersecretion of in vivo mucin. However, HST did not affect hypersecretion of in vivo mucin. Conclusion: These results suggest that CHT can not only affect the secretion of mucin but also the expression of the mucin gene and could be helpful for treating pulmonary disease caused by secretion of mucin.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.105-111
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• 1999

Nitric oxide (NO), a cellular messenger synthesized from L-arginine by NO synthase (NOS, EC.1.14.13.39), is considered to be a regulator of gastric secretion. In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat gastric chief cells. Treatment of chief cells with carba-chol resulted in an increase in the arginine conversion to citrulline, the amount of $NO_{x}$, the release of pepsine-gen, and the level of cGMP Especially, carbachol-stimulated increase of arginine to citrulline transformation, the amount of $NO_{x}$, cGMP level and the release of pepsinogen were partially reduced by the natural NOS inhibitor, $N^{G}$-monomethyl-L-arginine (MMA) and $N^{G}$, $N^{G}$-dimethyl-L-arginine (DMA). Furthermore, MMA- and DMA-induced decrease of pepsinogen secretion showed dose-dependent patters. Activation of NOS is one of the early events in receptor-mediated cascade of reactions in gastric chief cells and NO, not completely, but partially mediates gastric secretion. Agonist-stimulated pepsinogen secretion in chief cells has been considered to be mediated in adenosine 3',5'-cyclic monophosphate pathway and/or guanosine 3', 5'-cyclic monophosphate (cGMP) pathway. Taken together, the above results suggest that partial decrease of exocrine secretion following treatment of NOS inhibitor may result from the inactivation of NOS and subsequent guano- late cyclase, and NO/cGMP pathway may play a pivotal role in exocrine secretion.

• Journal of Microbiology and Biotechnology
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• 제9권5호
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• pp.576-581
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• 1999

Effects of signal sequences, protein sizes and dissolved oxygen on the secretion of human lysozyme from a recombinant yeast were experimentally characterized. The systems consisted of Saccharomyces cerevisiae host SEY2102 that was transformed with two different plasmids. These plasmids were identical with an exception to the plasmid pMC614, which contained the native yeast MFα1 sequence and the plasmid pMC632 with the non-native rat α-amylase signal sequence. The expression of human lysozyme was controlled by the ADHI promoter. The native yeast MFαl signal sequence was more efficient than the non-native rat α-amylase signal sequence in directing the secretion of human lysozyme. Lysozyme secreted with the α-amylase signal was retained inside the cells and released to the medium very slowly, thereby causing a lower cell growth rate and a decreased product secretion rate. Lysozyme was secreted more efficiently than invertase, which is an order of magnitude bigger in molecular size compared to lysozyme, which was under the direction of the MFαl signal sequence, suggesting that protein sizes may affect the secretion efficiency. When expressed in anaerobic conditions in the medium where the ADHI promoter was derepressed, the amount of lysozyme secreted was about twice higher than that of the aerobic culture. However, the secretion rates were identical. This result showed that the dissolved oxygen level may affect the efficiency of protein secretion only, and not the secretion rate of the product protein.

• 동의신경정신과학회지
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• 제12궈1호
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• pp.137-149
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• 2001

Cytokines are polypeptides which possess various biological properties affecting. host defense function and response to disease. Inflammatory cytokines, tumor necrosis $factor-{\alpha}$(TNF-${\alpha}$), interleukin(IL)-1 and IL-6 induce inflammation, fever, hypotension and pain when injected into animals or human subject. When glial cell cultures were prepared from neonatal mice or rats, astrocytes were reported to produce these inflammatory cytokines to viral infection, lipopolysaccharide(LPS), or cytokines. The purpose of this study was to investigate the regulatory effect of these cytokines secretion from primary cultures of rat astrocytes. Substance P(SP) can stimulate secretion of TNF-${\alpha}$ from astrocytes stimulated with LPS. Sesim-Tang significantly inhibited the TNF-${\alpha}$ secretion by astrocytes stimulated with SP and LPS. IL-1 has been shown to elevate TNF-${\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-${\alpha}$ secretion from primary astrocytes by Sesim-Tang. Treatment of Sesim-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of TNF-${\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Furthermore Sesim-Tang inhibited the IL-6 secretion by astrocytes stimulated with SP and LPS. The inhibitory effect of inflammatory cytokines by Sesim-Tang, observed in this study, might reflect an antiinflammatory activity and a reduction of various-type pains, fever etc. in the central nervous system.

• 미생물학회지
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• 제51권2호
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• pp.108-114
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• 2015

본 연구에서는 Streptomyces subrutilus P5의 생장과 세포내 외 철 함유 superoxide dismutase 활성을 비교 분석하여 철함유 superoxide dismutase의 분비 시점을 확인하고 분자 수준에서 이 효소의 분비에 관여하는 유전정보를 확인하고자 하였다. Streptomyces subrutilus P5의 균체 생장은 건체 중량을 측정하여 결정하였다. Glucose는 log phase에서 급격히 소모되어 24시간 후에 이르러 완전히 고갈되었다. 세포내의 철 함유 superoxide dismutase는 배양 후 3시간에 나타나며 세포외 철 함유 superoxide dismutase는 배양 후 7.5시간부터 나타난다. 따라서 superoxide dismutase는 용균에 의해서가 아니라 능동적인 분비기작에 의해서 세포 외로 분비된 것으로 추측할 수 있다. Streptomyces subrutilus P5의 sodF에는 signal peptide 유전정보가 존재하지 않았다. 그러나 sodF의 상류지역에서 다른 세균의 type III 분비단백질 유전자와 유사한 type III 분비상자가 발견되었다. Streptomyces 균주에서 type III 분비단백질이 존재할 가능성이 있음을 처음으로 제시하였다.

• Journal of Oral Medicine and Pain
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• 제26권1호
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• pp.17-25
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• 2001

The purpose of this study is to evaluate the relationship of menstrual cycle and halitosis by measuring the concentrations of Voltile Sulfur Compounds, secretion rate of unstimulated saliva, secretion rate of stimulated saliva and viscosity of saliva during the menstrual cycle. The subjects were 19 female dental students of Yonsei University who had relatively good alignment of the teeth. They hadn't taken antibiotics or oral contraceptive pills during the few months prior to the experiment, and they didn't have any dental caries involving the pulp or periodontal disease. Lady-$Q^{(R)}$(Alpain Korea, Korea), which confirms the ovulation using saliva, was used to find out the menstrual cycle of subjects. Their history was taken and their basal body temperature was measured. On the basis of these data, the amount of Volatile Sulfur Compounds, secretion rate of unstimulated saliva, secretion rate of stimulated saliva, viscosity of saliva were measured during 1 day of the proliferative phase, 3 days of ovulatory phase and 1 day of the luteal phase within the menstrual cycle. The results were as follows : 1. The amount of Volatile Sulfur Compounds, secretion rate of unstimulated saliva, secretion rate of stimulated saliva, and viscosity of saliva showed no statistically significant cyclic change during proliferative phase, ovulatory phase, and luteal phase(p<0.05). 2. Between the secretion rate of unstimulated saliva and secretion rate of stimulated saliva, there was significant correlation during proliferative phase and luteal phase(p<0.05) and there was no significant correlation during ovulatory phase but relatively close result was seen. 3. The amount of Volatile Sulfur Compounds during proliferative phase and luteal phase had statistically significant correlation(p<0.05). 4. Secretion rate of stimulated saliva during proliferative phase and ovulatory phase, proliferative phase and luteal phase, ovulatory phase and luteal phase had significant correlations (p<0.01).

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.667-674
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• 2017

Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and $1{\mu}M$) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) ($0.1{\mu}M$)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor ($AT_1R$) but not by an antagonist of $AT_2R$ or $AT_4R$. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate ($IP_3$) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) $10{\mu}M$ caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the $AT_1R$ and $PLC/IP_3/PKC$ pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.

• 대한수의학회지
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• 제44권4호
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• pp.497-505
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• 2004

The proliferation of mesangial cells has been associated with the development of diabetic nephropathy. The cell proliferation has been regulated by diverse growth factors. Among them, insulin like growth factors(IGFs) are also involved in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion and the relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in the mesangial cells. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. High glucose(25 mM) increased IGF-I and IGF-II secretion. High glucose-induced increase of IGF-I and IGF-II secretion were blocked by taurine($2{\times}10^{-3}$ M), N-acetyl cystein(NAC, $10^{-5}M$), or GSH($10^{-5}M$) (antioxidants), suggesting the role of oxidative stress. High glucose-induced secretion of IGF-I and IGF-II were blocked by H-7, staurosporine, and bisindolylmaleimide I(protein kinase C inhibitors). On the other hand, high glucose also increased lipid peroxide (LPO) formation in a dose dependent manner. In addition, high glucoseinduced stimulation of LPO formation was blocked by PKC inhibitors. These results suggest that PKC is responsible for the increase of oxidative stress in the action of high glucose-induced secretion of IGF-I and IGF-II in mesangial cells. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via PKCoxidative stress signal pathways in mesangial cells.

• Journal of Microbiology and Biotechnology
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• 제31권7호
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• pp.1035-1043
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• 2021

Although engineered Saccharomyces cerevisiae fermenting cellobiose is useful for the production of biofuels from cellulosic biomass, cellodextrin accumulation is one of the main problems reducing ethanol yield and productivity in cellobiose fermentation with S. cerevisiae expressing cellodextrin transporter (CDT) and intracellular β-glucosidase (GH1-1). In this study, we investigated the reason for the cellodextrin accumulation and how to alleviate its formation during cellobiose fermentation using engineered S. cerevisiae fermenting cellobiose. From the series of cellobiose fermentation using S. cerevisiae expressing only GH1-1 under several culture conditions, it was discovered that small amounts of GH1-1 were secreted and cellodextrin was generated through trans-glycosylation activity of the secreted GH1-1. As GH1-1 does not have a secretion signal peptide, non-conventional protein secretion might facilitate the secretion of GH1-1. In cellobiose fermentations with S. cerevisiae expressing only GH1-1, knockout of TLG2 gene involved in non-conventional protein secretion pathway significantly delayed cellodextrin formation by reducing the secretion of GH1-1 by more than 50%. However, in cellobiose fermentations with S. cerevisiae expressing both GH1-1 and CDT-1, TLG2 knockout did not show a significant effect on cellodextrin formation, although secretion of GH1-1 was reduced by more than 40%. These results suggest that the development of new intracellular β-glucosidase, not influenced by non-conventional protein secretion, is required for better cellobiose fermentation performances of engineered S. cerevisiae fermenting cellobiose.