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CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES

CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES
人肝细胞对甲状腺激素的细胞摄取
批准号:
3463406
负责人:
DAVID H SARNE
金额:
$9.27万
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-08-07 至 1991-07-31

项目摘要

项目成果

DAVID H SARNE的其他基金

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中文摘要
翻译
甲状腺激素(TH)进入细胞是一个关键,但 不太了解的过程。 TH进入细胞的改变可能 有助于甲状腺激素代谢的变化, 禁食,在重症患者(NTI),甲状腺功能减退症,并作为一个 毒品的后果。 TH进入细胞的改变已经被证实是 在异常TH血清结合蛋白的患者中描述 作为一种主要的遗传缺陷, 抗TH。 这些研究的长期目标是 阐明甲状腺进入的机制和调节 激素进入人体细胞,并评估其贡献, 临床问题。 将培养的人肝细胞Hep G2 因为它们保留了正常人类肝脏的许多特性 细胞,并允许控制实验条件。 将这些细胞与放射性碘标记的T3和T4孵育, 未标记的TH和无活性代谢物将建立,如果人 肝细胞具有TH的饱和摄取系统, 在生理浓度下具有功能性,并对活性物质具有特异性 日 用不同浓度的游离T3和T4孵育, 纯化白蛋白、甲状腺素结合前白蛋白(TBPA),以及 甲状腺素结合球蛋白(TBG)将指示这些蛋白质是否 促进TH的吸收。 用放射性碘孵育细胞 标记的白蛋白,TBPA和TBG将决定这些 血清蛋白特异性结合于人肝细胞。 血清异常者对示踪TH的摄取 TH结合蛋白将评估这些蛋白质是否改变了细胞的功能。 细胞摄取 TH与呋塞米和游离脂肪酸的孵育 酸将决定这些假定的TH抑制剂是否 与NTI中的血清蛋白结合也干扰细胞进入 理论产率 用细胞阻滞剂处理Hep G2细胞 ATP的产生将表明甲状腺的摄取是否 激素进入人体细胞是能量依赖的。 预处理 与抑制内吞作用的药物联合使用, 这一过程在人细胞摄取TH中很重要。 将从Hep G2细胞获得的膜制备物 结合不同浓度的标记和未标记T3 和T4来检测特定的膜受体。 孵育 用伊泊酸、胺碘酮和普萘洛尔标记TH, 如果它们通过竞争摄取而改变TH的细胞进入, 抑制脱碘或降低细胞ATP含量。 的 甲状腺功能低下对Hep G2细胞长期作用的影响 血清和血清与过量TH将确定是否甲状腺 激素状态可改变TH进入人体细胞。
英文摘要
The entry of thyroid hormone (TH) into cells is a critical, but poorly understood process. Alterations of TH entry into cells may contribute to changes in thyroid hormone metabolism during fasting, in severely ill patients (NTI), in hypothyroidism, and as a consequence of drugs. Altered entry of TH into cells has been described in patients with abnormal TH serum binding proteins and as a primary inherited defect producing generalized resistance to TH. The long term goal of these studies is to delineate the mechanisms and regulation of the entry of thyroid hormone into human cells and to evaluate its contributions to clinical problems. Cultured human hepatocytes, Hep G2, will be utilized as they retain many properties of normal human liver cells and allow experimental conditions to be controlled. Incubation of these cells with radioiodine labeled T3 and T4 with unlabeled TH and inactive metabolites will establish if human liver cells have saturable uptake systems for TH that are functional at physiologic concentrations, and specific for active TH. Incubation with varying concentrations of free T3 and T4 and purified albumin, thyroxine binding prealbumin (TBPA), and thyroxine binding globulin (TBG) will indicate if these proteins facilitate uptake of TH. Incubation of cells with radioiodine labeled albumin, TBPA, and TBG will determine whether these serum proteins are specifically bound to human liver cells. Uptake of tracer TH from serum of subjects with abnormal serum TH binding proteins will evaluate whether these proteins alter the cellular uptake. Incubation of TH with furosemide and free fatty acids will determine whether these postulated inhibitors of TH binding to serum proteins in NTI also interfere with cellular entry of TH. Treatment of Hep G2 cells with drugs which block cellular ATP generation will indicate whether the uptake of thyroid hormone into human cells is energy dependent. Pre-treatment with drugs which inhibit endocytosis will indicate whether this process is important in the uptake of TH by human cells. Membrane preparations obtained from the Hep G2 cells will be combined with varying concentrations of labeled and unlabeled T3 and T4 to detect specific membrane receptors. Incubation of labeled TH with ipodate, amiodarone and propranolol will evaluate if they alter cellular entry of TH by competing for uptake, inhibiting deiodination, or decreasing cellular ATP content. The effect of long term treatment of Hep G2 cells with hypothyroid serum and serum with excess TH will establish whether thyroid hormone status may alter the entry of TH into human cells.
期刊论文(5)
专著(0)
科研奖励(0)
会议论文
Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions.
对变体甲状腺素结合球蛋白(TBG)-圣地亚哥的测序揭示了两个核苷酸取代。
DOI: 10.1016/0925-4439(92)90105-v
发表时间: 1992
期刊: Biochimica et biophysica acta
影响因子: --
作者: [Bertenshaw,R, Sarne,D, Tornari,J, Weinberg,M, Refetoff,S]
通讯作者: Refetoff,S
Serum thyrotropin and prolactin in the syndrome of generalized resistance to thyroid hormone: responses to thyrotropin-releasing hormone stimulation and short term triiodothyronine suppression.
甲状腺激素普遍抵抗综合征中的血清促甲状腺素和催乳素:对促甲状腺素释放激素刺激和短期三碘甲状腺原氨酸抑制的反应。
DOI: 10.1210/jcem-70-5-1305
发表时间: 1990
期刊: The Journal of clinical endocrinology and metabolism
影响因子: --
作者: [Sarne,DH, Sobieszczyk,S, Ain,KB, Refetoff,S]
通讯作者: Refetoff,S
Limitations to the use of a sensitive assay for serum thyrotropin in the assessment of thyroid status.
在评估甲状腺状态时使用血清促甲状腺素敏感测定法的局限性。
DOI: --
发表时间: 1989
期刊: Archives of internal medicine
影响因子: --
作者: [Ehrmann,DA, Weinberg,M, Sarne,DH]
通讯作者: Sarne,DH
A new inherited abnormality of thyroxine-binding globulin (TBG-San Diego) with decreased affinity for thyroxine and triiodothyronine.
甲状腺素结合球蛋白(TBG-圣地亚哥)的一种新遗传异常,与甲状腺素和三碘甲状腺原氨酸的亲和力降低。
DOI: 10.1210/jcem-68-1-114
发表时间: 1989
期刊: The Journal of clinical endocrinology and metabolism
影响因子: --
作者: [Sarne,DH, Refetoff,S, Nelson,JC, Linarelli,LG]
通讯作者: Linarelli,LG
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
海外基金