Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea.
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.
Cells. 2022 Sep 1;11(17):2722. doi: 10.3390/cells11172722.
Primary cilia help to maintain cellular homeostasis by sensing conditions in the extracellular environment, including growth factors, nutrients, and hormones that are involved in various signaling pathways. Recently, we have shown that enhanced primary ciliogenesis in dopamine neurons promotes neuronal survival in a Parkinson's disease model. Moreover, we performed fecal metabolite screening in order to identify several candidates for improving primary ciliogenesis, including L-carnitine and acetyl-L-carnitine. However, the role of carnitine in primary ciliogenesis has remained unclear. In addition, the relationship between primary cilia and neurodegenerative diseases has remained unclear. In this study, we have evaluated the effects of carnitine on primary ciliogenesis in 1-methyl-4-phenylpyridinium ion (MPP)-treated cells. We found that both L-carnitine and acetyl-L-carnitine promoted primary ciliogenesis in SH-SY5Y cells. In addition, the enhancement of ciliogenesis by carnitine suppressed MPP-induced mitochondrial reactive oxygen species overproduction and mitochondrial fragmentation in SH-SY5Y cells. Moreover, carnitine inhibited the production of pro-inflammatory cytokines in MPP-treated SH-SY5Y cells. Taken together, our findings suggest that enhanced ciliogenesis regulates MPP-induced neurotoxicity and inflammation.
初级纤毛通过感知细胞外环境中的条件(包括参与各种信号通路的生长因子、营养物质和激素)来帮助维持细胞内稳态。最近,我们已经表明,多巴胺神经元中增强的初级纤毛发生促进了帕金森病模型中的神经元存活。此外,我们进行了粪便代谢物筛选,以鉴定出几种可改善初级纤毛发生的候选物,包括左旋肉碱和乙酰左旋肉碱。然而,肉碱在初级纤毛发生中的作用仍不清楚。此外,初级纤毛与神经退行性疾病之间的关系仍不清楚。在这项研究中,我们评估了肉碱对 MPP 处理细胞中初级纤毛发生的影响。我们发现左旋肉碱和乙酰左旋肉碱均可促进 SH-SY5Y 细胞中的初级纤毛发生。此外,肉碱增强纤毛发生可抑制 MPP 诱导的 SH-SY5Y 细胞中线粒体活性氧过度产生和线粒体碎片化。此外,肉碱可抑制 MPP 处理的 SH-SY5Y 细胞中促炎细胞因子的产生。综上所述,我们的研究结果表明,增强的纤毛发生可调节 MPP 诱导的神经毒性和炎症。