Chen Min, Tian Jiaming, Jia Buyun, Wang Meng, Han Anqi, Zhu Jiming, Tian Shasha, Gao Xiaoming, Li Baikun, Li Qinglin, Li Shanshan
Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China.
School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 4. doi: 10.1007/s00210-025-04348-9.
Glycolysis, a fundamental pathway in cellular energy metabolism, exhibits dysregulation that is intricately linked to the pathogenesis of Parkinson's disease (PD). Although the compensatory upregulation of aerobic glycolysis helps sustain ATP levels, its precise effects on dopaminergic neurons remain poorly understood. This study investigated the mechanism of rotenone-induced injury in PC12 cells and explored the potential protective effect of gastrodin. We found that rotenone exposure significantly enhanced glycolysis, with increased lactate production, lactate dehydrogenase (LDH) activity and decreased pyruvate concentrations. However, gastrodin treatment effectively attenuated rotenone-induced glycolysis, normalizing lactate production, LDH activity, and pyruvate levels. Furthermore, gastrodin inhibited the increase in glycolytic enzymes hexokinase 2(HK2), Pyruvate kinase M2(PKM2), and Lactate dehydrogenase A(LDHA) levels induced by rotenone. Notably, the combination of the HK2-specific inhibitor 2-DG with gastrodin demonstrated synergistic effects in inhibiting rotenone-induced glycolysis in PC12 cells. These findings collectively indicated that HK2-mediated aberrant glycolysis plays a pivotal role in rotenone-induced cell death, and that gastrodin confers neuroprotection through modulation of this metabolic pathway.
糖酵解是细胞能量代谢的基本途径，其失调与帕金森病（PD）的发病机制密切相关。尽管有氧糖酵解的代偿性上调有助于维持ATP水平，但其对多巴胺能神经元的确切影响仍知之甚少。本研究探讨了鱼藤酮诱导PC12细胞损伤的机制，并探究了天麻素的潜在保护作用。我们发现，鱼藤酮暴露显著增强了糖酵解，乳酸生成增加、乳酸脱氢酶（LDH）活性升高，丙酮酸浓度降低。然而，天麻素处理有效地减弱了鱼藤酮诱导的糖酵解，使乳酸生成、LDH活性和丙酮酸水平恢复正常。此外，天麻素抑制了鱼藤酮诱导的糖酵解酶己糖激酶2（HK2）、丙酮酸激酶M2（PKM2）和乳酸脱氢酶A（LDHA）水平的升高。值得注意的是，HK2特异性抑制剂2-DG与天麻素联合使用在抑制鱼藤酮诱导的PC12细胞糖酵解方面具有协同作用。这些发现共同表明，HK2介导的异常糖酵解在鱼藤酮诱导的细胞死亡中起关键作用，天麻素通过调节这一代谢途径发挥神经保护作用。
