缺乏激素结合活性的葡萄糖皮质体受体结合在缺乏ATP的细胞核中
Nature
|December 4, 1986
概括
腺三酸盐 (ATP) 枯竭导致葡萄糖皮质体受体进入一个不活跃的,不活跃的,不活跃的区域.
科学领域:
- 细胞生物学 细胞生物学
- 分子内分泌学分子内分泌学
- 生物化学 生物化学
背景情况:
- 葡萄糖皮质体受体 (GR) 结合对于细胞对葡萄糖皮质体的反应至关重要.
- 细胞中的ATP耗尽导致GR结合能力的丧失.
- 在缺少ATP的细胞中存在一种不活跃的"无受体"形式,这是假设的,但没有直接观察到.
研究的目的:
- 提供直接证据,证明存在的零受体.
- 为了研究ATP枯竭细胞中零受体的局部化和丰富性.
主要方法:
- 使用了WEHI-7小鼠胸腺瘤细胞.
- 使用特定于葡萄糖皮质体受体的单克隆抗体.
- 在正常和ATP贫乏的细胞条件下评估受体局部化和结合.
主要成果:
- 在缺乏ATP的细胞的细胞核中检测到零受体.
- 在缺乏ATP的细胞中,零受体的数量与正常细胞中受体的数量相当.
- 这表明受体存在,但是在一个不活跃的,非结合性构造.
结论:
- 直接证明了零受体的存在,这是葡萄糖皮质体受体的非活性形式.
- 零受体位于核中,即使在激素结合丢失时,也存在大量.
- 这些发现支持了ATP水平调节葡萄糖皮质体受体活性激素结合状态的模型.
相关概念视频
Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...


