MECHANISM OF BREFELDIN A ACTION

BREFELDIN A 的作用机制

• 批准号: 3768892
• 负责人: J W YEWDELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3768892
• 关键词: Golgi apparatus; antifungal antibiotics; antineoplastic antibiotics; chemical conjugate; chemical structure function; endoplasmic reticulum; fluorescent dye /probe; protein transport; tissue /cell culture

Brefeldin A (BFA) is a fungal metabolite with a broad range of biological activities, including the anti-fungal and anti-tumor activities. In the past few years there has been tremendous interest in its effect on cells, since it has been found to have the unique ability to interfere with vesicular trafficking. Among its effects, it has the ability to disperse the Golgi complex, returning at least some of its components to the endoplasmic reticulum (ER). BFA also prevents newly synthesized proteins destined for the cell surface from leaving the ER. To better understand the mechanism of BFA action we conjugated it to two fluorescent dyes and studied its intracellular localization. Both conjugates maintained their biological activity, and both specifically localized to the ER and Golgi complex in live or aldehyde-fixed cells. The interaction with intracellular membranes is probably due to interaction with lipids as it is abolished by detergent extraction of lipids. These conjugates are the first dyes that bind the ER and Golgi complex without binding other prominent membrane bound compartments and should prove useful as probes for the these organelles in living cells. Their ability to stain the ER of fixed cells will be of great use as markers of the ER in cytochemical studies. Finally, the interaction of BFA with the ER and GC membranes might be critical to its biological activity.

布雷菲德菌素A（Brefeldin A，BFA）是一种真菌代谢产物，具有广泛的生物活性。 生物活性，包括抗真菌和抗肿瘤 活动 在过去的几年里， 在其对细胞的影响，因为它已被发现具有独特的 干扰囊泡运输的能力。 在其影响中， 它有分散高尔基复合体的能力， 内质网（ER）的一些组成部分。 BFA还 阻止新合成的蛋白质进入细胞表面， 离开急诊室 为了更好地了解BFA的作用机制， 将其与两种荧光染料偶联， 本地化 两种缀合物均保持其生物活性， 并且都特异性地定位于ER和高尔基复合体， 固定细胞。 与细胞内膜的相互作用是 可能是由于与脂质的相互作用，因为它被洗涤剂消除 提取脂质。 这些共轭物是第一个结合 ER和高尔基体复合体不结合其它突出膜结合物 隔室，并应证明这些细胞器的探针有用 在活细胞中。 它们对固定细胞的ER染色的能力将是 在细胞化学研究中作为ER的标记物非常有用。 最后， BFA与ER和GC膜的相互作用可能是关键的 它的生物活性。