Fyn 激酶调节高糖（HG）处理的动物和细胞模型中的多巴胺能神经元凋亡。
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment.
机构信息
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
Chongqing Medical University, Chongqing, 400010, China.
出版信息
BMC Mol Cell Biol. 2021 Dec 4;22(1):58. doi: 10.1186/s12860-021-00398-y.
BACKGROUND
High glucose (HG) is linked to dopaminergic neuron loss and related Parkinson's disease (PD), but the mechanism is unclear.
RESULTS
Rats and differentiated SH-SY5Y cells were used to investigate the effect of HG on dopaminergic neuronal apoptotic death. We found that a 40-day HG diet elevated cleaved caspase 3 levels and activated Fyn and mTOR/S6K signaling in the substantia nigra of rats. In vitro, 6 days of HG treatment activated Fyn, enhanced binding between Fyn and mTOR, activated mTOR/S6K signaling, and induced neuronal apoptotic death. The proapoptotic effect of HG was rescued by either the Fyn inhibitor PP1 or the mTOR inhibitor rapamycin. PP1 inhibited mTOR/S6K signaling, but rapamycin was unable to modulate Fyn activation.
CONCLUSIONS
HG induces dopaminergic neuronal apoptotic death via the Fyn/mTOR/S6K pathway.
背景
高葡萄糖（HG）与多巴胺能神经元丢失和相关的帕金森病（PD）有关，但机制尚不清楚。
结果
使用大鼠和分化的 SH-SY5Y 细胞来研究 HG 对多巴胺能神经元凋亡死亡的影响。我们发现，40 天的 HG 饮食可使大鼠黑质中裂解的 caspase 3 水平升高，并激活 Fyn 和 mTOR/S6K 信号通路。体外，6 天的 HG 处理可激活 Fyn，增强 Fyn 与 mTOR 之间的结合，激活 mTOR/S6K 信号通路，并诱导神经元凋亡死亡。Fyn 抑制剂 PP1 或 mTOR 抑制剂 rapamycin 均可挽救 HG 的促凋亡作用。PP1 抑制 mTOR/S6K 信号通路，但 rapamycin 不能调节 Fyn 的激活。
结论
HG 通过 Fyn/mTOR/S6K 通路诱导多巴胺能神经元凋亡死亡。
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