• 대한두경부종양학회지
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• 제18권2호
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• pp.142-149
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• 2002

본 연구에서는 FRTL-5 갑상선세포에서 Protein phosphatase type 1(PP-1)과 type 2A(PP-2A) 효소의 억제제인 okadaic acid에 의한 apoptosis 유도 기전에 대하여 이해하고자 하였다. FRTL-5 갑상선세포에 다양한 농도($10{\sim}80nmol$)의 okadaic acid를 처리 한 후 caspase 3와 $PLC-{\gamma}1$ 분절을 확인 한 결과 40nmol 농도에서부터 caspase 3활성과 $PLC-{\gamma}1$ 분절이 나타남을 확인하였다. Okadaic acid에 의한 apoptosis 유도 기전을 조사한 결과 anti-apoptotic 기능이 있는 Bcl-2 단백질 발현은 미약하게 감소하였으나 Bcl-xL은 농도 의존적으로 급격한 감소를 보였다. Caspase 3 효소활성을 저해하는 IAP 단백질 중 cIAP2는 okadaic acid에 영향을 받지 않았으나 cIAP1과 XIAP 단백질 발현은 농도 의존적으로 감소하였다. Okadaic acid에 의한 apoptosis 유도는 caspase 3 의존적인 기전을 보였다. Caspase 3 특이억제제를 okadaic acid와 동시에 처리 시 apoptosis가 억제되었으며 $PLC-{\gamma}1$ 단백질의 절단 현상도 방지되었다. Caspase 3의 활성을 유도하는 cytochrome c의 유리는 okadaic acid처리 농도에 의존적으로 유리하였다. 결론적으로, okadaic acid에 의한 apoptosis 유도는 caspase 3 의존적이며, Bcl-2와 IAP family 단백질 감소현상에 의하여 야기되는 것으로 생각된다.

• 대한의생명과학회지
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• 제14권1호
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• pp.59-62
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• 2008

This experiment was performed to study the effect of TSH (thyroid-stimulating hormone) on the expression of endoplasmic reticulum (ER) chaperones in the rat thyrocytes FRTL-5 cells. Although the expressions of ER membrane kinases (ATF6, IRE1 and PERK) were specially enhanced under absence of TSH, no remarkable up- or down regulations of ER chaperones (BiP, CHOP and Calnexin) were detected by TSH. We firstly report here that TSH by dose up-regulated expression of ER membrane kinases in FRTL-5 culture thyrocytes.

• 대한한방내과학회지
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• 제26권2호
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• pp.398-408
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• 2005

Objective: Graves' disease encompasses hyperthyroidism and diffused goiter associated with auto-antibodies to the thyroid stimulating hormone(TSH) receptors. In clinical environment, treatments of Graves' disease have many side effects such as recurrence and hypothyroidism. We've studied the effects of Sipyukmiyukieum on DNA synthesis, cAMP synthesis, and MHC-class II expression of FRTL-5 thyroid cells were studied. Methods: DNA synthesis was investigated by using BrdU staining and cAMP synthesis by ELISA kit, and expression of $interferon-{\gamma}$ activated MHC class II by Flow cytometer. Results: After introduction of Sipyukmiyukieum, significant inhibition of DNA synthesis. cAMP synthesis, and expression of $interferon-{\gamma}$ activated MHC class II of FRTL-5 thyroid cells was observed. Conclusions: Judging from these results, Sipyukmiyukieum has potential as a potent herbal treatment for inhibiting the enlargement of goiter, synthesis of abnormal thyroidal hormones, and autoimmuine responses of Graves' disease.

• The Korean Journal of Physiology and Pharmacology
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• 제8권4호
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• pp.195-200
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• 2004

Ghrelin is a newly discovered peptide, which is released from the stomach and neurons in the hypothalamic arcuate nucleus (ARC), and potently stimulates growth hormone release and food intake. In the present study, we investigated the effect of ghrelin on $[Ca^{2+}]_i$ in thyroid FRTL-5 cells. Ghrelin (5 nM) increased $[Ca^{2+}]_i$ and TSH (1 unit/l) had an additive effect on $[Ca^{2+}]_i$ when extracellular normal solution was 1.1mM $Ca^{2+}$ containing Coon's modified Ham's F12 medium. When $Ca^{2+}-free$ medium containing 2 mM EGTA replaced the above normal solution, ghrelin also induced a similar rise in $[Ca^{2+}]_i$. In the middle of $[Ca^{2+}]_i$ increment by ghrelin, nifedipine $(1\;{\mu}M)$, nickel $(100\;{\mu}M)$ and $La^{3+}\;(100\;{\mu}M)$ had no effect on $[Ca^{2+}]_i$. After endoplasmic reticulum was depleted by cyclopiazonic acid $(CPA;10\;{\mu}M)$, ghrelin caused no visible change on $[Ca^{2+}]_i$ in $Ca^{2+}-free$/2 mM EGTA solution. These results suggest that ghrelin can increase $[Ca^{2+}]_i$ through endoplasmic reticulum in thyroid FRTL-5 cells.

• 대한한방내과학회지
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• 제27권3호
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• pp.653-663
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• 2006

Objective : Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder associated with autoantibodies to the TSH receptor. The clinical features of Graves' disease are goiter and hypermetabolic symptoms induced by excessive hormones. Antithyroid drug therapy is the first-line treatment for Graves' disease in Korea, Japan and European countries. Yet in spite of a long period and high-dose of treatment, it is hard to achieve remission because of adverse effects, frequent recurrence and resistance to antithyroid drugs. Recently, it has been reported that the abnormal thyroid hormone and clinical symptoms of Graves' disease were reduced by Ahnjeonbaekho-tang (AJBHT). Methods : To investigate the effectiveness and action mechanism of AJBHT, we studied the influence of AJBHT on FRTL-5 thyroid cell proliferation, DNA synthesis and expression of T4, TSH, cAMP, Tg and TPO mRNA. Results : AJBHT significantly inhibited the FRTL-5 cell proliferation, DNA synthesis, T4 synthesis, cAMP production and the expression of Tg mRNA in comparison with control and MMI. Conclusions : These results suggest that AJBHT may inhibit the cell proliferation and DNA synthesis by regulating the cAMP, and suppress the T4 synthesis by modulating Tg mRNA expression and cAMP synthesis, and that it may be useful agent for treating the goiter and hormone abnormality of Graves' disease.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1988년도 제27차 춘계학술대회
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• pp.141.1-141.1
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• 1988

• 생명과학회지
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• 제9권1호
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• pp.76-83
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• 1999

Endoplasmic reticulum (ER)내에 단백질의 folding과 안정화에 관여하는 단백질을 molecular cha-perone이라고 한다. GRP94 역시 ER내에 존재하는 molecular chaperone으로 알려지고 있지만 갑상선세포에서 단백질의 folding에 관여한다는 증거는 아직 불충분하다. 본 설험은 molecular chaperone을 세포내에서 overexpression시킬 수 있는 system을 확립하였다. 그 중에서 GRP94가 단백질의 folding에 직접적으로 관여한다는 증거를 얻기 위하여, endogenous GRP94를 code한 cDNA를 overexpression vector에 의해서 forced expression시킴으로 신생thyroglobulin의 folding에 직접적으로 관여하는 증거를 immun-oprecipitation으로 증명하였다.

• 생명과학회지
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• 제10권2호
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• pp.150-156
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• 2000

This experiment was performed to evaluate the effect of TSH (thyroid-stimulating) on the ERp29 (endoplasmic reticulum resident 29 kDa protein) gene expression in the rat thyrocytes of FRTL-5 cells. Although ERp29 mRNA was constantly expressed, its expression began to increase remarkably from 10-9 M TSH. and its maximum expression was at 5×10-9 M TSH (about 3.5 fold). On the other hand, the effect of TSH on the abundance of ERp29 mRNA started within 6 h, and peaked at 8 h (about 2.5 fold). Actinomycin D (transcription inhibitor) strongly blocked this effect while cycloheximide (translation inhibitor) did not. The half-life of ERp29 mRNA was about 4.5 h in the presence or absence of TSH that was not affected by the stability of ERp29 mRNA. The effect of TSH on the ERp29 gene expression was specific, while other growth factors (transfferin, insulin, and hydrocortisone) did not alter its expression. Our data indicate for the first time that the expression of ERp29 is regulated transcriptionally by TSH in the thyrocytes.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2002년도 제38회 학술심포지움
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• pp.61-67
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• 2002

ERp29는 ER chaperone의 한 종류이지만 아직까지 세포내에서 그 기능은 명확하지 않다. 배양 갑상선세포 (FRTL-5)에서 ERp29의 발현은 TSH (thyroid stimulating hormone) 의존적으로 조절되며, ERp29가 과발현된 세포에서는 ERp29-ER chaperone가 긴밀한 관계를 유지하여 분비단백질인 Thyroglobulin의 분비량이 약 30% 증가되었다.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1988년도 제27차 춘계학술대회
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• pp.140.2-141
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• 1988