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      • 갑상선 세포에서 전사보조활성인자인 CBP와 CIITA의 인터페론-감마 활성 부위에 대한 조절 : CBP and CIITA on GAS(Interferon- γ Activated Site)-Mediated Transcription in Thyroid Cells

        채수흥,홍우정,김군순,조영석,김도희,김현진,구본정,송민호,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

        Background : In the previous stuides, we identified that the interferon-r activated sequence (GAS) in the 5-flanking region of rat ICAM-1 gene is major element for interferon-r-inducible expression of the gene in rat thyroid cells, FRTL-5. We here, investigated the role of transcriptional coactivators, CBP(CREB binding protein) and CⅡTA (class Ⅱ transactivator) in the modulation of the activity of GAS which could interacts with signal transducers and activators of transcription-1 and 3 (STAT1 and STAT3). Methods : The expression of CBP RNA and protein were quantitated in FRTL-5 after stimulation with interferon-r (IFN-r), thyroid stimulating hormone (TSH), forskolin and methimazole. Direct association of CBP with STAT were analyzed by immunoprecipitation. The transcriptional roles of CBP and CⅡTA in the regulation of GAS were assessed by the cotransfection with their expression vectors with reporters; 5-deletion constructs of rat ICAM-1 promoter or 8xGAS-luc constructs, into FRTL-5 thyroid cells. Results : The level of CBP RNA and protein were not changed by the treatment with TSH, IFN-r, forskolin and methimazole in FRTL-5, FRT and BRL liver cells. The CBP could be directly associated with STAT1. Furthermore, the overexpression of CBP significantly increases the both promoter activities; rat ICAM-1 gene promoter which has GAS element and 8xGAS-luc cassette constructs. However, the cotransfection of CⅡTA decreased the constitutive and CBP-mediated transactivation of rat ICAM-1 promoter and 8xGAS-luc cassette constructs. Conclusion : We identified that the two tanscriptional coactivators; CBP and CⅡTA has differential roles in the regulation of transcriptional activity of GAS drived promoter. CBP increases the GAS activity through the direct binding with STAT1, but CⅡTA inhibited the CBP-mediated transactivation of GAS activity.

      • 당뇨병에 동반된 고지혈증에 대한 연구

        김영건,주원찬,원진호,한희정,채수흥,김현진,김윤 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.2

        Background. Diabetes mellitus is combined with other metabolic disfunction, especially dyslipidemia. Dyslipidemia is the risk factor of cardiovascular disease. So we studied about dyslipidemia associated DM. Method. A total 169 subjects were studied. This study was performed by review of medical records retrospectively. Results. The mean level of triglyceride and total cholesterol was 315.2mg/dI, 249.3mg/dl respectively. The most common type of dyslipidemia was pure hypertriglyceridemia. Whether obese, hypertensive, have cardiovascular disease or not the level of triglyceride and total cholesterol was not different from another. The triglyceride of patients with fatty liver was significantly higher(370.4mg/dl) than that(296.4mg/dl) of patients without fatty liver. The total cholesterol of patients with overt proteinuria(30mg/day<daily urinary protein<300mg/day) was significantly higher(276.3mg/dl) than that(239.9mg/dl) of patients without proteinuria.

      • 폐경후 여성에서 에스트로겐, 이프리플라본, 칼시토닌 투여에 따른 골대사 표지자의 변화

        노흥규,주원찬,한희정,채수흥,송민호 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.2

        The measurements of metabolic bone markers are important for assesment of risks of osteoporotic fractures and efficacy of anti-osteoporotic treatment in postmenopausal women. We measured bone mineral densites, serum total alkaline phosphatases, and osteocalcin levels in estrogen replacement group(n=13), lpriflavone group(n=8), Calcitonin gruop(n=8) and untreated group(n=50). We used the dual energy X-ray absorptiometry for measurement of bone mineral densities in vertebra, used the p-nitrophenylphosphate and radioimmunoassay for serum alkaline phosphatase and serum osteocalcin, repectively. We compared the metablic hone markers, serum alkaline phosphatase, and osteocalcin between differrent treatment groups and analyzed the correlation between bone mineral densities with above metahlic bone markers. The treatment groups; estrogen, ipriflavone, and calcitonin groups showed significant low osteocalcin (p<0.05) levels but total alkaline phosphatase levels showed no significant difference compare to untreated group (p>0.05). There were no statistical significance of serum osteocalcin and alkaline phosphatase levels beween Ipriflavonc and untreated control group. Calcitonin group showed significant high alkaline phoshatase levels compare to untreated group(p<0.05) but osteocalcin levels showed no significant difference to untreated group. In conclusion, The biochemical bone markers such total alkaline phosphatase and serum osteocalcin are useful markers for the assesment of anti-osteoporotic treatment efficacy in postmenopausal women and reflect the high bone turnover in untreated postmenopausal women

      • HMG-CoA 환원효소 억제제에 의한 ICAM-1 유전자의 발현조절

        김현진,정효균,홍우정,김군순,조영석,김도희,채수흥,구본정,송민호,노흥규,김영건 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

        Background : ICAM-1 act as one of major adhesion molecules in the atherosclerotic lesion. ICAM-1 expression is mainly regulated at the level of transcription and depend on IFN-γ signal transduction pathway in which the STAT1 transcrption factor is a critical intermediate. IFN-γreceptor not only initiates tyrosine 701 phosphorylation of STAT1 by Jak1 and Jak2, but also phosphorylates serine 727 through the activation of Raf-1/MAP kinases. HMG-CoA reductase inhibitors have anti-atherosclertic effects, beyond normalization of hypercholesterolemia, by directly acting on endothelial cells, macrophages and vascular smooth muscle cells. HMG-CoA reductase inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibition posttranslational farnesylation and geranyl-geranylation processing of small GTP-binding preoteins and inhibition of normal signaling activities. Method : We made several 5'-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after transfection into ECV304 cells and smooth muscle cells. We checked the level of total and phosphorylated STAT1 protein by immunoblot analysis using specific antibodies. Results : Lovastatin inhibits IFN-γ-induced ICAM-1 gene expression in the ECV304cell. The cells pretreated with PD98059, MEKK inhibitor showed significantly low ICAM-1 RNA induction with IFN-γ stimulatio. IFN-γ induced phosphorylation of tyrosine 701 was not significantly changed by the pretreatment of lovastatin. But lovastatin suppresses IFN-γ-induced phosphorylation of ERK1/ERK2 which are responsible for the seine 727 phosphorylation in STAT1. Conclusion : We showed that HMG-CoA reductase inhibitors, lovastatin, suppresses IFN-γ mediated ICAM-1 gene expression through the inhibition of transcription. HMG-CoA reductase inhibitor suppresses IFN-γ-induced phosphorylation of serine 727 in STAT1 through the modulation of MAP kinases.

      • SCOPUSKCI등재

        자가면역성 갑상선 질환 환자에서 혈청내 수용성 Fas 치의 변동

        김현진,노흥규,송민호,한희정,주원찬,신재규,채수흥 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.2

        The Changes of soluble Fas levels in Patients with Autoimmune Thyroid Diseases Backgroud: Apoptosis was observed in thyroid tissue from Hashimoto disease but not those from Graves disease. Recently Fas and Fas ligand interactions among thyrocytes were suggested to development of clinical hypothyroidism in Hashimoto disease.Soluble Fas produced as the form lacking the tranmembrane domain due to alternative splicing, is supposed to inhibit Fas-Fas ligand interaction and blocks Fas mediated apoptosis. Methods: In tbis study, we measured serum soluble Fas to determine the possible involvement of this molecule in the autoimmune thyroid disease by enzyme linked immunosorbant assay in 29 patients with Graves disease, 30 patients with Hashimotos disease and 19 normal controls. Results: Compared with normal subjeets (4.26 +- 1.00 U/mL), soluble Fas was not increased in patients with Graves disease (4.23 +- 1.14 U/mL, p$gt;0.05) but it was increased in throtoxic Graves patients (4.70 +- 1.26 U/mL, p$lt;0.05) compared to euthyroid Graves (3.72 +- 0.73 U/mL, p$lt;0.05) and normal subjects (4.26 +- 1.00 U/mL, p$lt;0.05). The euthyroid and hypothyroid patients with Hashimoto disease showed low soluble Fas levels, 2.94 +- 0.54 U/mL and 2.74 U/mL, respectively compare to the patients with Graves disease and normal subjects. The thyroid hormone levels to (T3 T4 and free T4) showed positive correlation with the serum titers of antithyroid autoantibodies, antithyroglobuin antibodies, antiperoxidase antibodies and thyrotropin binding inhibitor immunoglobulins. Conclusion: We found that the patients with thyrotoxic Graves disease had increased level of serum soluble Fas and the patients with Hashimoto disease showed low levels of soluble Fas compared to normal controls. Increased soluble Fas in Graves disease suggests increased expression of alternatively spliced Fas mRNA variant and decreased soluble Fas in Hashimoto disease suggests decreased Fas mRNA variant and increased full length membrane Fas, so these findings are related to the promotion of apoptosis of thyroid cells during autoimmune reaction in Hashimotos disease. (J Kor Soc Endocrinol 14:293-300, 1999)

      • SCOPUSKCI등재

        갑상선 세포에서 전사보조활성인자인 CBP와 CIITA는 인터페론-감마 활성 부위에 대하여 서로 다른 조절 작용을 나타낸다

        유순희,김현진,김도희,김영건,송민호,노흥규,박수정,김호,박은신,채수흥,권오유,한희정 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.3

        Background: In the previous studies, we identified that the interferon-γ activated sequence (GAS) in the 5-flanking region of rat ICAM-1 gene is major element for interferon-y-inducible expression of the gene in rat thyroid cells, FRTL-5. We here, investigated the role of transcriptional coactivators, CBP (CREB binding protein) and CIITA (class II transactivator) in the modulation of the activity of GAS which could interacts with signal transducers and activators of transcription-1 and 3 (STAT1 and STAT3). Methods: The expression of CBP RNA and protein were quantitated in FRTL-5 after stimulation with interferon-y (IFN-γ), thyroid stimulating hormone (TSH), forskolin and methimazole. Direct association of CBP with STAT were analyzed by irnmunoprecipitation. The transcriptional roles of CBP and CIITA in the regulation of GAS were assessed by the cotransfection with their expression vectors with reporters; 5-deletion constructs of rat ICAM-1 promoter or 8xGAS-luc constructs, into FRTL-5 thyroid cells. Results: The level of CBP RNA and protein were not changed by the treatment with TSH, IFN-y, forskolin and methimazole in FRTL-5, FRT and BRL liver cells. The CBP could be directly associated with STAT1. Furthernmore, the overexpression of CBP significantly increases the both promoter activities; rat ICAM-1 gene promoter which has GAS element and 8xGAS-luc cassette constructs. However the cotransfection of CI1TA decreased the constitutive and CBP-mediated transactivation of rat ICAM-1 promoter and SxGAS-luc cassette constructs. Conclusion: We identified that the two transcriptional coactivators; CBP and CIITA has differential roles in the regulation of transcriptional activity of GAS drived promoter. CBP increases the GAS activity through the direct binding with STATl, but CIITA inhibited the CBP-mediated transactivation of GAS activity (J Kor Soc Endocrinol 14:493-504, 1999).

      • SCOPUSKCI등재

        갑상선 기능변화에 따른 혈청 Leptin치의 변화

        김현진,김영건,노흥규,송민호,김윤,한희정,주원찬,원진호,채수흥 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.2

        Background: Leptin, the product of ob gene, is an important circulating hormone for the regulation of homeostasis of body weight and enegy expenditure. There was a previous reports that thyroid hormone is one of regulating factors of leptin gene expression in vitro. The aim of this study was designed to evaluate the role of thyroid hormone levels in the regulation of circulating leptin concentrations in human. Methods: A total 16S subjects were studied; 76 patients with Graves disease, 49 patients with Hashimoto disease and 43 control sujjects. The correlation between thryoid hormone and leptin levels were analyzed and serum leptin levels were compared among the groups which was classified by thyroid functional status. Serum leptin concentratios were measured by radioimmunoassay. Results: There were no significant differences in serum leptin levels between the groups of control, Graves disease and Hashimoto disease. The hypothyroid groups of Graves disease which was induced by excessive antithyroid drug treatment showed significant low levels(5.6 +-2.8 ng/mL) compared to control(9.6 +- 5.2 ng/ml) and thyrotoxic groups(10.0 +- 5,0 ng/mL) Conclusion: The hypothyroid patients showed low levels of serum leptin concentrations it may indicate that thyroid horrnone play a role in the appropriate secretion of leptin in human. (J Kor Soc Endocrinol 14:372-, 1999)

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