사람 비만세포주에서 Clozapine과 Fluoxetine에 의한 케모카인 및 케모카인 수용체의 상이한 발현

유영민,김종우,조정제,임강현 대한생물치료정신의학회 2001 생물치료정신의학 Vol.7 No.2

Objectives : It has been suggested that the immune system has a role in the pathophsiology of neuropsychiatric diseases. There are some reports that clozapine and fluoxetine affect on cytokine networks. Recently, it has been known that chemokines have chemotactic effect, and modulate a number of biological responses including the process of inflammation and the maintenance of CNS homeostasis. In the present study, we investigated the effect of clozapine or fluoxetine on the expression of chemokines and their receptors. Methods : Human mast cells(HMC-1) was incubated with phorbol myristate acetate(PMA, 100ng/㎖) and calcium ionophore A23187(350ng/㎖) for 3 hours. Colzapine(10^-7M) or fluoxetine(10^-7M) were pretreated for 1 hour. RT-PCR was performed for the detection of expression of various chemokines and chemokine receptors. Results : after treatment of clozapine, the expression of MCP-1, MIP-1β, CCR3,CXCR2, CXCR3 and CXCR4 were lower than the PMA/Ca ionophore-treated group, while the expression of MIP-1α, RANTES and IL-8 were not changed. However, fluoxetine was not affected the changes of expression of various chemokines and chemokine receptors. Conclusion : This result indicates that clozapine may affect on the expression of chemokines and chemokine receptors. Therefore, this study could, in part, provide the important basic data on the explanation of side effects of clozapine, such as fever and pancreatitis.

Visualization and Quantification of Radiochemical Purity by Cerenkov Luminescence Imaging

Ha, Yeong Su,Lee, Woonghee,Jung, Jung-Min,Soni, Nisarg,Pandya, Darpan N.,An, Gwang Il,Sarkar, Swarbhanu,Lee, Won Kee,Yoo, Jeongsoo American Chemical Society 2018 ANALYTICAL CHEMISTRY - Vol.90 No.15

<P>Determination of radiochemical purity is essential for characterization of all radioactive compounds, including clinical radiopharmaceuticals. Radio-thin layer chromatography (radio-TLC) has been used as the gold standard for measurement of radiochemical purity; however, this method has several limitations in terms of sensitivity, spatial resolution, two-dimensional scanning, and quantification accuracy. Here, we report a new analytical technique for determination of radiochemical purity based on Cerenkov luminescence imaging (CLI), whereby entire TLC plates are visualized by detection of Cerenkov radiation. Sixteen routinely used TLC plates were tested in combination with three different radioisotopes (<SUP>131</SUP>I, <SUP>124</SUP>I, and <SUP>32</SUP>P). All TLC plates doped with a fluorescent indicator showed excellent detection sensitivity with scanning times of less than 1 min. The new CLI method was superior to the traditional radio-TLC scanning method in terms of sensitivity, scanning time, spatial resolution, and two-dimensional scanning. The CLI method also showed better quantification features across a wider range of radioactivity values compared with radio-TLC and classical zonal analysis, especially for β<SUP>-</SUP>-emitters such as <SUP>131</SUP>I and <SUP>32</SUP>P.</P> [FIG OMISSION]</BR>

석면함유 슬레이트 지붕 물받이 퇴적물 중 석면 섬유 함유율

임지현,한솔민,김현석,신유민,박시은,허정윤,김민영,장봉기 순천향대학교 기초과학연구소 2022 순천향자연과학연구 논문집 Vol.28 No.1,2

This study attempted to determine the degree of asbestos release from the aging slate roof by comparing the asbestos content in the slate roof rain gutter with a colored steel plate (tin plate) over the slate roof. Four slate roof houses located in Haengmok-ri, Asan-si, Chungcheongnam-do, and one house constructed with a colored steel plate on the slate roof were selected to collect the sediment of the roof rain gutter. The asbestos fiber content was calculated by a point counting method using a polarization microscope after pretreatment with conversion treatment and hydrochloric acid treatment. The average asbestos content of the four slate roof rain gutter were 1.89%. However, asbestos was not detected in the Slate covering roof rain gutter, which were constructed on the slate roof. Asbestos fiber content was the highest at 2.89% in the slate roof rain gutter installed in 1976, followed by 2.44% in 1953. From the above results, it is necessary to minimize secondary damage as asbestos fibers released from slate roof houses to the surrounding atmosphere or leaked from slate roofs as rainwater may cause soil pollution and seriously affect residents' health. Although covering with colored steel plates (tin plates) has been shown to prevent the leakage of asbestos fibers to some extent, it is believed that a policy alternative to remove the slate roof as soon as possible is needed to solve the fundamental problem.

Melatonin Suppresses Autophagy Induced by Clinostat in Preosteoblast MC3T3-E1 Cells

Yoo, Yeong-Min,Han, Tae-Young,Kim, Han Sung MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

<P>Microgravity exposure can cause cardiovascular and immune disorders, muscle atrophy, osteoporosis, and loss of blood and plasma volume. A clinostat device is an effective ground-based tool for simulating microgravity. This study investigated how melatonin suppresses autophagy caused by simulated microgravity in preosteoblast MC3T3-E1 cells. In preosteoblast MC3T3-E1 cells, clinostat rotation induced a significant time-dependent increase in the levels of the autophagosomal marker microtubule-associated protein light chain (LC3), suggesting that autophagy is induced by clinostat rotation in these cells. Melatonin treatment (100, 200 nM) significantly attenuated the clinostat-induced increases in LC3 II protein, and immunofluorescence staining revealed decreased levels of both LC3 and lysosomal-associated membrane protein 2 (Lamp2), indicating a decrease in autophagosomes. The levels of phosphorylation of mammalian target of rapamycin (p-mTOR) (Ser2448), phosphorylation of extracellular signal-regulated kinase (p-ERK), and phosphorylation of serine-threonine protein kinase (p-Akt) (Ser473) were significantly reduced by clinostat rotation. However, their expression levels were significantly recovered by melatonin treatment. Also, expression of the Bcl-2, truncated Bid, Cu/Zn- superoxide dismutase (SOD), and Mn-SOD proteins were significantly increased by melatonin treatment, whereas levels of Bax and catalase were decreased. The endoplasmic reticulum (ER) stress marker GRP78/BiP, IRE1α, and p-PERK proteins were significantly reduced by melatonin treatment. Treatment with the competitive melatonin receptor antagonist luzindole blocked melatonin-induced decreases in LC3 II levels. These results demonstrate that melatonin suppresses clinostat-induced autophagy through increasing the phosphorylation of the ERK/Akt/mTOR proteins. Consequently, melatonin appears to be a potential therapeutic agent for regulating microgravity-related bone loss or osteoporosis.</P>

Melatonin suppresses cyclosporine A-induced autophagy in rat pituitary GH3 cells

Yoo, Yeong-Min,Jeung, Eui-Bae Blackwell Publishing Ltd 2010 Journal of pineal research Vol.48 No.3

<P>Abstract: </P><P>Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the induction of chronic nephrotoxicity including endoplasmic reticulum (ER) stress in tubular cells. Recently, it was reported that autophagy is induced by ER stress and serves to alleviate the associated deleterious effects. In the current study, CsA treatment (0–100 <I>&mgr;</I><SMALL>M</SMALL>) decreased cell survival of rat pituitary GH3 cells in a dose-dependent manner. At concentrations ranging from 1.0 to 10 <I>&mgr;</I><SMALL>M</SMALL>, CsA induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-I and LC3-II. Cells treated with 2.5 <I>&mgr;</I><SMALL>M</SMALL> CsA exhibited cytoplasmic vacuolation, indicating that CsA induces autophagy in rat pituitary GH3 cells. In the presence of 1.0–10 <I>&mgr;</I><SMALL>M</SMALL> CsA, the expression of catalase decreased while that of the ER stress markers, ER luminal binding protein (BiP) and inositol-requiring enzyme 1 alpha (IRE1&agr;), increased as compared those levels in untreated cells. These results suggested that CsA-induced autophagy is dependent on ER stress. To determine whether melatonin would protect cells against CsA-induced autophagy, we treated rat pituitary GH3 cells with melatonin in the presence of CsA. Melatonin treatment (100 and 200 <I>&mgr;</I><SMALL>M</SMALL>) suppressed autophagy induced by 2.5 and 5 <I>&mgr;</I><SMALL>M</SMALL> CsA. Furthermore, co-treatment with 100 <I>&mgr;</I><SMALL>M</SMALL> melatonin inhibited LC3-II expression, and increased catalase and phosphorylated p-ERK levels in the presence of 2.5 and 5 <I>&mgr;</I><SMALL>M</SMALL> CsA. BiP and IRE1&agr; expression in melatonin-co-treated cells was superior to that in cells treated with 2.5 and 5 <I>&mgr;</I><SMALL>M</SMALL> CsA alone. Thus, melatonin suppresses CsA-mediated autophagy in rat pituitary GH3 cells.</P>

<i>Calbindin-D28k</i> in the Brain Influences the Expression of Cellular Prion Protein

Yoo, Yeong-Min,Jeung, Eui-Bae Hindawi 2018 Oxidative medicine and cellular longevity Vol.2018 No.-

<P>The phenotypes of <I>calbindin-D9k</I>- (<I>CaBP-9k</I>-) knockout (KO), <I>calbindin</I>-<I>D28k</I>- (<I>CaBP-28k</I>-) KO, and <I>CaBP-9k/28k</I>-KO mice are similar to those of wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we investigated the expression of cellular prion protein (PrP<SUP>C</SUP>) in the brains of <I>CaBP-9k</I>-, <I>CaBP-28k</I>-, and <I>CaBP-9k/28k</I>-KO mice. PrP<SUP>C</SUP> expression was significantly upregulated in the brain of all three strains. Levels of phospho-Akt (Ser473) and phospho-Bad (Ser136) were significantly elevated, but those of phospho-ERK and phospho-Bad (Ser155 and 112) were significantly reduced in the brains of <I>CaBP-9k</I>-, <I>CaBP-28k</I>-, and <I>CaBP-9k/28k</I>-KO mice. The expressions of the Bcl-2, p53, Bax, Cu/Zn-SOD, and Mn-SOD proteins were decreased in the brains of all KO mice. Expression of the endoplasmic reticulum marker protein BiP/GRP78 was decreased, and that of the CHOP protein was increased in the brains of those KO mice. To identify the roles of <I>CaBP-28k</I>, we transfected PC12 cells with siRNA for <I>CaBP-28k</I> and found increased expression of the PrP<SUP>C</SUP> protein compared to the levels in control cells. These results suggest that <I>CaBP-28k</I> expression may regulate PrP<SUP>C</SUP> protein expression and these mice may be vulnerable to the influence of prion disease.</P>

Melatonin-induced estrogen receptor &agr;-mediated calbindin-D9k expression plays a role in H₂O₂-mediated cell death in rat pituitary GH3 cells

Yoo, Yeong-Min,Jeung, Eui-Bae Blackwell Publishing Ltd 2009 Journal of pineal research Vol.47 No.4

<P>Abstract: </P><P>Calbindin-D9k (CaBP-9k) is a 9-kDa polypeptide possessing two calcium-binding sites that is expressed in the mammalian intestine, uterus, and pituitary gland. The factors regulating the expression of the estrogen receptor (ER) and CaBP-9k in the pituitary gland are currently unknown. In this study, we investigated whether the ER and CaBP-9k expression are regulated by melatonin during H<SUB>2</SUB>O<SUB>2</SUB>-induced cell death in rat pituitary GH3 cells. Cell survival increased by approximately 27–36% in H<SUB>2</SUB>O<SUB>2</SUB> plus melatonin compared to H<SUB>2</SUB>O<SUB>2</SUB> alone, and CaBP-9k expression was augmented by treatment with H<SUB>2</SUB>O<SUB>2</SUB> plus melatonin. These results suggest that the increase in cell survival and the melatonin-induced CaBP-9k expression may play a role in protecting cells against H<SUB>2</SUB>O<SUB>2</SUB>-mediated cell death. This result is also consistent with the increase in CaBP-9k expression leading to rises in p-ERK and p-Bad (S112). Over-expression of <I>CaBP-9k</I> caused an increase in p-ERK. ER&agr; expression was higher in H<SUB>2</SUB>O<SUB>2</SUB> plus melatonin-treated cells compared to those treated with H<SUB>2</SUB>O<SUB>2</SUB> alone, while ER&bgr; expression was not. Also, ER&agr; in the nuclear fraction increased in the presence of melatonin and decreased in the presence of ICI 182 780 or ICI 182 780 plus melatonin. The relative binding affinity of ER&agr; for melatonin was higher than that of ER&bgr;, suggesting that melatonin has the potential to preferentially bind ER&agr;. In conclusion, these results indicate that melatonin may increase CaBP-9k expression through ER&agr;.</P>

제왕절개술시 Propofol 목표농도주입의 평가와 약동학적 변화

민상기,유은숙,김진수,길호영,원종진,한상건 대한정맥마취학회 2001 정맥마취 Vol.5 No.2

Background: Propofol has been used for the induction and maintenance agent of general anesthesia for cesarean section, but the pharmacokinetics of propofol will be different from in case of non-pregnancy. In order to evaluate the performance of computer-assisted continuous infusion (CACI) system and pharmacokinetic changes of propofol during cesarean section under general anesthesia, we measured the plasma concentrations of propofol, and compared those with the predicted plasma concentrations. Methods: Sixty pregnant women who received cesarean section under general anesthesia were studied. After the titration of adequate post-delivery target propofol concentration with bispectral index in twenty pregnant women, forty women were randomly assigned into the two different groups. In group I, after preoxygenation, anesthesia was induced with thiopental 4 ㎎/㎏ and succinylcholine 1 ㎎/㎏, and intubation was done. Vecuronium 0.1 ㎎/㎏ Ⅰ.Ⅴ. was administered for muscle relaxation, and mechanical ventilation was maintained with EtCO_2 between 30-35 ㎜Hg. Anesthesia was maintained with N_2O/O_2 (2:2 L/min) with enflurane before delivery, meanwhile, 3.5 ㎍/㎖ propofol target-controlled infusion (TCI) and 1.0 ng/㎖ fentanyl TCI with air/O_2 (2:2 L/min) were maintained after delivery. In group Ⅱ, anesthesia was induced with propofol (2.0 ㎎/㎏) and maintained with 3.5 ㎍/㎖ propofol TCI and air/O_2 (2:2 L/min), and after delivery the target concentration of propofol 5.0 ㎍/㎖ and 1.0 ng/㎖ fentanyl TCI were maintained. The bispectral index were monitored perioperatively. The plasma propofol concentrations were measured at 10 minute intervals and the predicted concentrations were evaluated with the performance errors (PE). Results: The target concentrations (Cp, 95% confidence interval) that could maintain 50% and 95% of patients hemodynamically stable with the bispectral index within 40 - 60 after delivery were 3.7 (3.20 - 3.92) ㎍/㎖ and 5.0 (4.67 - 5.74) ㎍/㎖ for propofol when it had been started since the induction of anesthesia. In group 1, the measured concentrations of propofol at 10 minute intervals after delivery were, 2.61 ± 0.74, 2.51 ± 0.60 and 2.23 ± 0.64 ㎍/㎖, and the median absolute performance errors (MAPE's) were 25.4%, 28.7% and 37.1% respectively. In group Ⅱ, the measured concentration at delivery was 1.94 ± 0.54 ㎍/㎖, and after delivery 2.38 ± 1.22, 2.11 ± 0.97 and 1.86 ± 1.04 ㎍/㎖ and the MAPE's were 39.1%, 52.8%, 60.2% and 63.0% respectively. The maximally increased bispectral index after the induction of anesthesia until delivery was significantly higher in group 1. Conclusions: It was concluded that CACI using the pharmacokinetic model of propofol for nonpregnancy could not provide the predicted target plasma concentrations with a sufficient accuracy in case of patients who received cesarean section under general anesthesia. But the measured propofol concentrations were enough to maintain an adequate sedation level for the cesarean section under general anesthesia with monitoring the bispectral index.

Melatonin-induced calbindin-D9k expression reduces hydrogen peroxide-mediated cell death in rat pituitary GH3 cells

Yoo, Yeong-Min,Jeung, Eui-Bae Blackwell Publishing Ltd 2010 Journal of pineal research Vol.48 No.2

<P>Abstract: </P><P>In this study, we investigated whether calbindin-D9k (CaBP-9k) expression was regulated by melatonin during hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>)-induced cell death in rat pituitary GH3 cells. CaBP-9k expression was increased by melatonin in a dose- and time-dependent manner, indicating that CaBP-9k expression is regulated by melatonin. Cell survival was increased approximately 27–30% where H<SUB>2</SUB>O<SUB>2</SUB>-treated cells (0.25 or 0.5 m<SMALL>M</SMALL>) were also incubated with 1 m<SMALL>M</SMALL> melatonin, when compared with H<SUB>2</SUB>O<SUB>2</SUB> alone or H<SUB>2</SUB>O<SUB>2</SUB> plus 0.5 m<SMALL>M</SMALL> melatonin. This result was consistent with 4,6-diamidino-2-phenylindole staining. CaBP-9k expression was also augmented by co-treatment with H<SUB>2</SUB>O<SUB>2</SUB> and 1 m<SMALL>M</SMALL> melatonin, suggesting a functional relationship between increased cell death and melatonin-induced CaBP-9k expression during H<SUB>2</SUB>O<SUB>2</SUB>-mediated apoptosis. Bcl-2-associated protein expression increased following treatment with H<SUB>2</SUB>O<SUB>2</SUB> alone, whereas Bcl-2 expression was elevated following treatment with melatonin alone, or H<SUB>2</SUB>O<SUB>2</SUB> plus melatonin. The expression of p53 was depressed by treatment with melatonin alone, or co-treatment with H<SUB>2</SUB>O<SUB>2</SUB> plus melatonin. These results correlated with CaBP-9k expression levels and activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway. Knockdown of CaBP-9k expression using a small inhibitory RNA resulted in an elevation of H<SUB>2</SUB>O<SUB>2</SUB>-induced cell death, whereas cell survival was increased in cells that overexpressed CaBP-9k, providing additional evidence that the induction of CaBP-9k expression may be associated with survival signaling during H<SUB>2</SUB>O<SUB>2</SUB>-mediated oxidative cell death. CaBP-9k appears to interact with p53, suggesting a possible role for this interaction in cell proliferation and cell cycle progression.</P>

Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes

Yoo, Yeong-Min,Jang, Su Kil,Kim, Gwang-Hoon,Park, Jung-Youl,Joo, Seong-Soo Elsevier 2016 JOURNAL OF BIOMEDICAL RESEARCH -ELSEVIER- ENGLISH Vol.30 No.4

<P><B>Abstract</B></P><P>Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in <I>in vitro</I> and <I>in vivo</I> models. Splenocytes, CD4<SUP>+</SUP>, and naïve CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation (CD28 and p21) and the melatonin receptor (MT1A and MT1B) were assessed. The T cell activation-related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT1A, and MT1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4<SUP>+</SUP> T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4<SUP>+</SUP> T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.</P>