Identification of ginkgolide targets in brain by photoaffinity-labeling
| Autor: | Gregg G. Gundersen, Koji Nakanishi, Doina M. Mihai, Francesca Bartolini, Akira Kawamura, Ilyas Washington, Milica Tesic Mark |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
macromolecular substances Photoaffinity Labels Pharmacology Biochemistry Hippocampus Microtubules Article Microtubule polymerization Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Microtubule Detyrosination Drug Discovery Animals Humans Ginkgolides Photoaffinity labeling biology Ginkgo biloba Organic Chemistry biology.organism_classification 030104 developmental biology chemistry Ginkgolide Molecular Medicine 030217 neurology & neurosurgery |
| Popis: | Ginkgolides are terpene trilactones in Ginkgo biloba, a popular medicinal herb for memory disorders. Although ginkgolides are known for various neurobiological effects, their macromolecular target in brain is unknown. In this work, we employed benzophenone derivatives of ginkgolides to identify their binding target in brain. Photolabeling of bovine hippocampus homogenates identified a series of α-tubulin isotypes. Selective photolabeling of α-tubulin over β-tubulin, which is equally abundant in brain, suggested that ginkgolides might modulate microtubule biology differently than typical microtubule-binding agents, such as taxol. In fact, ginkgolide A did not affect microtubule polymerization or cell proliferation; instead, it inhibited detyrosination of α-tubulin and reorientation of microtubule-organizing centers. Taken together, the current findings indicate that ginkgolides constitute a new class of microtubule-binding agents with distinct effects on α-tubulin biology. |
| Databáze: | OpenAIRE |
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