Reorganization of Mitochondrial Function and Architecture in Response to Plant-Derived Alkaloids: Anatabine, Anabasine, and Nicotine, Investigated in SH-SY5Y Cells and in a Cellular Model of Parkinson's Disease

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-09-04 DOI:10.1111/cns.70571

Dominika Malińska, Karolina Drabik, Bernadeta Michalska, Jarosław Walczak, Małgorzata Partyka, Monika Prill, Jędrzej Szymański, Paulina Patalas-Krawczyk, Karolina Piecyk, Jerzy Duszyński, Mariusz R. Więckowski, Joanna Szczepanowska

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引用次数: 0

Abstract

Aims

Nicotine, anatabine, and anabasine are the most prevalent alkaloids in Nicotiana species. While nicotine is the main addictive ingredient in tobacco products, it was also shown to have neuroprotective properties. Mitochondria appear to be one of the targets of nicotine in the cell. These multifunctional organelles are also the first responders to various cellular stresses. Thus, we characterized the impact of tobacco alkaloids on these organelles.

Methods

We investigated the effects of structurally similar alkaloids, anatabine, anabasine, and nicotine, on mitochondrial function in SH-SY5Y neuroblastoma cells under basal conditions and in the presence of rotenone, a mitochondrial stressor commonly used to model the cellular pathology underlying Parkinson's disease.

Results

We observed changes in mitochondrial behavior, including hyperpolarization, alterations in mitochondrial network morphology, increased mitochondrial turnover rates, and upregulation of mitochondrial biogenesis regulators. The profiles of changes induced by particular alkaloids slightly differed; however, they shared many features with the stress response observed upon treatment with rotenone. Interestingly, the effects of the alkaloids and rotenone were not additive. Moreover, some parameters altered by rotenone were normalized upon cotreatment with the alkaloids.

Conclusions

The results indicate that the investigated alkaloids stimulate mitochondrial stress adaptation. Despite structural similarity, they act through slightly different mechanisms.

Abstract Image

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在SH-SY5Y细胞和帕金森病细胞模型中，线粒体功能和结构重组对植物源生物碱：安纳他滨、安纳他滨和尼古丁的响应

目的烟碱、阿那他碱和阿那他碱是烟碱中最常见的生物碱。虽然尼古丁是烟草产品中主要的成瘾性成分，但它也被证明具有神经保护作用。线粒体似乎是细胞中尼古丁的目标之一。这些多功能细胞器也是各种细胞应激的第一反应者。因此，我们表征了烟草生物碱对这些细胞器的影响。我们研究了结构相似的生物碱，阿那他滨、阿那他滨和尼古丁，在基础条件下和鱼藤酮存在下对SH-SY5Y神经母细胞瘤细胞线粒体功能的影响。鱼藤酮是一种线粒体应激源，通常用于模拟帕金森病的细胞病理学。结果我们观察到线粒体行为的变化，包括超极化、线粒体网络形态的改变、线粒体周转率的增加和线粒体生物发生调节因子的上调。不同生物碱引起的变化谱略有不同；然而，它们与鱼藤酮治疗后观察到的应激反应有许多共同特征。有趣的是，生物碱和鱼藤酮的作用并不是相加的。此外，鱼藤酮与生物碱共处理后，鱼藤酮改变的一些参数归一化。结论生物碱具有促进线粒体应激适应的作用。尽管结构相似，但它们的作用机制略有不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.