• 한국식품영양과학회지
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• 제44권5호
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• pp.649-656
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• 2015

무지개송어 아가미상피세포를 이용하여 cortisol에 의해 유도된 세포 손상에 대항하는 아연의 보호 효과를 연구하였다. 24시간 동안 cortisol에 노출된 세포들은 농도 의존적으로 LDH 방출이 증가하였고, 세포 생존율은 감소하였다. 아연($100{\mu}M$ $ZnSO_4$) 처리에 의해 이와 같은 영향이 감소하였고, 아연은 cortisol에 의해 유도된 caspage-3 활성, 즉 apoptosis에 대항하여 세포를 보호하였다. Cortisol에 의해 유도된 세포 사멸, LDH 방출과 caspase-3 활성은 glucocorticoid 수용체의 길항제인 Mifepristone(RU-486) 처리에 의해 차단되었는데, 이것은 세포 손상이 cortisol과 관련이 있다는 것을 제안하였다. 더하여 cortisol에 의해 유도된 세포 손상 모델에서 MT, GST 그리고 G6PD와 같은 항산화 유전자 발현에 대한 아연의 영향을 연구했다. MTA, MTB, GST 그리고 G6PD mRNA 수준은 아연과 cortisol을 각각 단독 처리에 의해 그리고 아연과 cortisol을 동시 처리에 의해 증가하였다. 이와 같은 증가는 아연이나 cortisol 단독 처리보다는 $100{\mu}M$ $ZnSO_4$와 $1{\mu}M$ cortisol을 동시에 처리했을 때 MTA, MTB, GST 그리고 G6PD mRNA 수준이 더 높았다. 아연 처리에 의해 세포 내 자유 아연 농도가 증가하였고, 이와 같은 반응은 cortisol과 아연을 함께 처리했을 때 세포 내 자유 아연 농도가 더 증가하였다. 결론적으로 아연 처리는 간접적인 항산화 활성을 통해 cortisol에 의해 유도 세포독성 및 apoptosis를 저해하였다.

• 대한약리학회지
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• 제32권1호
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• pp.83-91
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• 1996

본 연구에서는 Hydrocortisone이 적출 흰쥐 관류 부신에서 histamine에 의한 카테콜아민 (CA) 분비작용에 대한 영향을 관찰하고자 시도하였으며, 얻어진 연구 결과는 다음과 같다. Histamine (150ug)은 부신정맥내로 주입시 현저한 CA 분비작용을 나타내었다. 이러한 histamine의 CA 분비작용은 천연 글루코콜티코이드인 hydrocortisone (30uM)이나 합성 글루코콜티코이드인 dexamethasone (30uM)을 각각 20분간 전처치한 후에 현저히 증강되었다. Hydrocortisone에 의한 histamine의 CA 분비의 증강작용은 inositol trisphosphate 수용체 억제제인 heparin (3.56U/ml)으로 천처치시 뚜렷이 억제되었으나 adenylate cyclase의 강력한 활성화제인 forskolin (0.2uM)으로 전처치시 현저히 강화되었다. 이상과 같은 실험 결과를 종합한 결과, hydrocortisone (글루코콜티코이드)은 흰쥐 적출관류 부신에서 histamine의 CA 유리작용을 증강시킬 수 있으며, 이는 부신수질 크롬친화성 세포에서 inositol phosphate 뿐만 아니라 cyclic AMP의 축적작용과 관련성이 있는것으로 사료된다.

• Animal Bioscience
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• 제35권8호
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• pp.1235-1249
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• 2022

Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.

• 생물정신의학
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• 제8권1호
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• pp.3-19
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• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• Animal cells and systems
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• 제1권1호
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• pp.115-121
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• 1997

To precisely analyze the role of ovarian steroids in the regulation of laminin chain gene expression in mouse uterine tissues, the ovariectomized mouse model was used. Ovariectomized mice received a single injection of steroid hormones and total RNA was isolated from whole uterine tissues. Messenger RNA levels of each laminin chain (A, 81, and 82) were determined by competitive RT-peR procedures. Estradiol decreased mRNA levels of laminin 81 chain about two-fold, and 82 chain rather moderately. Estradiol-induced inhibition of laminin 81 and 82 chain mRNA levels were completely blocked by pretreatment with estrogen receptor antagonist tamoxifen. Estriol, a short acting estrogen which cannot induce hyperplastic responses of rodent uterine tissues, also showed an inhibitory effect on 81 and 82 chain mRNA levels, while estrone, an inactive estrogen, failed to influence either 8 chain mRNA levels. Effects of steroids on A chain mRNA level were quite different from those on 8 chains. Laminin A chain mRNA level was slightly increased by estradiol treatment, but negatively affected by progesterone. Progesterone treatment greatly increased both 8 chain mRNA levels, but slightly decreased A chain mRNA level compared to the control. The effect of progesterone on laminin chain-specific mRNA levels was further increased by co-injection of estradiol in a time-dependent manner. Progesterone-induced 81 and 82 chain mRNA transcription was inhibited by RU486, a synthetic anti-progesterone /anti-glucocorticoid. The present study demonstrates for the first time that steroids are able to regulate laminin gene expression in mouse uterine tissues, indicating that steroid-regulated laminin gene expression is involved in uterine growth and probably differentiation.

• 생물정신의학
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• 제26권2호
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• pp.88-93
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• 2019

Objectives Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia. Methods Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models). Results The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16-2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11-2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13-2.10, p = 0.0067). Conclusions This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

• Animal cells and systems
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• 제14권2호
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• pp.99-114
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• 2010

With the consensus sequence information of the serum glucocorticoid-induced protein kinase-1 (SGK1) phosphorylation site {R-X-R-X-X-(S/T)$\Phi$; where $\Phi$ is any hydrophobic amino acid}, we noticed that the transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, harbors the putative SGK1 phosphorylation site (on its Ser 824). We have demonstrated that TRPV4 is an SGK1 authentic substrate protein, with the phosphorylation on the Ser 824 of TRPV4 by SGK1. Further, using TRPV4 mutants (S824A and S824D), we noted that the modification of the Ser 824 activates its $Ca^{2+}$ entry, and sensitizes the TRPV4 channel to 4-$\alpha$-phorbol 12,13-didecanoate (4-${\alpha}PDD$) or heat, simultaneously enhancing its active state. Additionally, we determined that the modification of the Ser 824 controls both its plasma membrane localization and its protein interactions with calmodulin. Thus, we have proposed herein that phosphorylation on the Ser 824 of TRPV4 is one of the control points for the regulation of its functions.

• 한국식품영양학회지
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• 제30권4호
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• pp.673-680
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• 2017

Fludarabine, a chain terminating anti-cancer drug, is a purine analogue that causes DNA strand breaks in normal cells. In this study, we determined if A. melanocarpa and Korean red ginseng extract mixture reduce cytotoxicity of fludarabine. Treatment of HaCaT cells with $10{\mu}M$ of fludarabine for 24 hours decreased cell viability and increased DNA strand breaks. Treatment of A. melanocarpa and Korean red ginseng extract mixture for 24 hours increased cell viability as compared with single extract treatment. The protective effect of these extracts on cell activity increased in a concentration-dependent manner. DNA strand breaks induced by fludarabine decreased as concentration of extract mixture increased. p-H2AX level, a marker of DNA strand breakage, decreased depending on the concentration of extract mixture. The effect of mixed extract of A. melanocarpa and Korean red ginseng on DNA damage is due to the anti-oxidative effect of A. melanocarpa and signal transmission through glucocorticoid receptor upon binding of saponin of Korean red ginseng.

• 동의신경정신과학회지
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• 제32권2호
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• pp.111-127
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• 2021

Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

• 생명과학회지
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• 제32권3호
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• pp.256-262
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• 2022

옥시스테롤은 담즙산 합성 동안 일련의 효소 반응에 의해 생성된 콜레스테롤의 산화물로써, 콜레스테롤과 유사하게 세포내 영역으로 빠르게 이동하여 면역 세포 반응, 지질 대사 및 콜레스테롤 항상성과 같은 다양한 세포 과정을 조절한다. 글루코코르티코이드 수용체(GR), 에스트로겐 수용체(ER) 및 간 X 수용체(LXR)와 같은 종류의 핵 수용체는 여러 조직에서 옥시스테롤에 의해 조절될 수 있다. 가장 풍부한 옥시스테롤인 27-하이드록시콜레스테롤(27-OHC)은 조직 특이적 방식에 의해 에스트로겐 수용체 활성을 활성화하거나 억제하기 때문에 선택적 에스트로겐 수용체 조절자로 규명되었다. 특히 27-하이드록시콜레스테롤이 동맥 경화증 플라크에서 많이 발견되고 대식세포가 거품 세포로 변형되는 것을 가속화하기 때문에 동맥 경화증 발병에 기여하는 것이 분명해 보이나, 다른 연구들에서는 27-하이드록시콜레스테롤이 간 및 지방 조직을 포함한 다양한 대사 기관에 미치는 영향에 대해 반대 의견이 존재한다. 따라서 본 총설을 통해 대사 조직에서의 27-하이드록시콜레스테롤 역할에 대한 논의와 함께, 죽상 동맥 경화증 및 대사 증후군에 영향을 주는 27-하이드록시콜레스테롤의 세부 기전에 대해 논의하고자 한다.