9-cisレチノ酸は,レチノイドX受容体の高親和性リガンドである
R A Heyman1, D J Mangelsdorf, J A Dyck
1Ligand Pharmaceuticals, Inc., San Diego, California 92121.
Cell
|January 24, 1992
まとめ
研究者らは,レチノイドX受容体 (RXR) の強力なリガンドとして9-cisレチノ酸 (RA) を発見した. この新しいホルモンは,生物の中に存在し,信号伝達におけるレチノイド代謝の重要性を強調しています.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- バイオケミストリー バイオケミストリー
背景:
- オールトランスレチノ酸 (RA) はレチノ酸受容体 (RAR) とレチノイドX受容体 (RXR) の活性を調節する.
- オールトランスRAがRXRを結合できないことは,より高い親和性を持つ潜在的代謝産物を示唆しています.
研究 の 目的:
- 以前の観測で示唆された高親和性RXRリガンドを特定するために.
- 新しいシグナリング分子の生成におけるレチノイド代謝の役割を調査する.
主な方法:
- RXRリガンドを特定するための実験的アプローチ.
- トランスフェクションアッセイは,リガンドの効能を決定する.
- 高アフィニティ・バインディング・アッセイ.
- 細胞培養と組織分析 (肝臓,腎臓) で,9-cis RA.を検出する.
主要な成果:
- RXR.の高親和性リガンドとして9-cis RAを特定した.
- 9-cis RAは,トランスフェクションアッセイにおいて,オールトランスRAよりも最大40倍の効能を示した.
- 培養細胞,肝臓,腎臓における9-cis RAの内生的な産生と存在が確認されました.
結論:
- 9-cis RAは,RXRを高 afinityで結合する新しい,生物学的活性ホルモンです.
- レチノイド代謝は,新しいホルモン生産を通じて新しいシグナル伝達経路を生成する上で重要な役割を果たします.
- この発見は,レチノイド信号伝達とその治療的可能性を理解するための新しい道を開く.
さらに関連する動画
05:03Quantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography
Published on: December 27, 2024
08:18Methodology for Studying Interactions of Vitamin A Membrane Receptors and Opsin Protein with their Ligands in Generating the Retinylidene Protein
Published on: October 4, 2024
関連する概念動画
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
01:31Transducer 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:
01:25Drug-Receptor Interaction: Agonist
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
01:29The Two-State Receptor Model
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
The binding affinity of a drug determines its interaction with one...