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微管蛋白与Δ-四氢大麻酚相互作用的结构变化:体外和理论研究。

Structural changes of tubulin by interacting with Δ-tetrahydrocannabinol: in-vitro and theoretical studies.

作者信息

Mohammadkhani Mina, Jarah Mostafa, Gholami Dariush, Riazi Gholamhossein, Rezazadeh Hadi

机构信息

Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.

Cinna Gen Medical Biotechnology Research Center, Alborz University of Medical Science, Karaj, Iran.

出版信息

BMC Neurosci. 2025 Jul 30;26(1):47. doi: 10.1186/s12868-025-00957-5.

Abstract

BACKGROUND

There is growing evidence of the contribution of microtubule dynamics to dendritic spine changes, synaptic plasticity, axonal transportation, and cell polarity. Besides, one of the well-studied effects of Cannabis on human behavior is memory disability. As Δ-tetrahydrocannabinol (Δ-THC) is the most pivotal chemical of Cannabis, we investigated the effect of Δ-THC on microtubule dynamicity and the structural study of tubulin (microtubule monomer).

RESULTS

Our results show that Δ-THC changes microtubule dynamicity compared to the control group. The turbidity assay results demonstrated that Δ-THC reduces microtubule polymerization in a concentration-dependent manner. Circular Dichroism spectroscopy also studied the structural changes of the purified tubulin, which revealed significant changes in the secondary structure of the tubulin. Furthermore, Silico studies predicted one binding site for Δ-THC on β-tubulin.

CONCLUSIONS

We concluded that Δ-THC could reduce the microtubule's stability, which may conversely affect brain function by microtubule dynamic changes caused by secondary structural changes of tubulin and preventing tubulin-tubulin interaction.

摘要

背景

越来越多的证据表明,微管动力学对树突棘变化、突触可塑性、轴突运输和细胞极性有重要作用。此外,大麻对人类行为的一个深入研究的影响是记忆障碍。由于Δ-四氢大麻酚(Δ-THC)是大麻中最关键的化学物质,我们研究了Δ-THC对微管动力学的影响以及微管蛋白(微管单体)的结构研究。

结果

我们的结果表明,与对照组相比,Δ-THC改变了微管动力学。比浊法测定结果表明,Δ-THC以浓度依赖的方式降低微管聚合。圆二色光谱也研究了纯化微管蛋白的结构变化,结果显示微管蛋白的二级结构有显著变化。此外,计算机模拟研究预测了Δ-THC在β-微管蛋白上的一个结合位点。

结论

我们得出结论,Δ-THC可降低微管的稳定性,这可能通过微管蛋白二级结构变化引起的微管动力学变化以及阻止微管蛋白-微管蛋白相互作用,反过来影响脑功能。

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