Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment

Changhong Tan,Xi Liu,Wen Zhou,Xiaoshuai Zhang,Jin Jiang,Lifen Chen,Hui Wang,Wuxue Peng,Yangmei Chen,Lijuan Mo

doi:10.1186/s12860-021-00398-y

Abstract

BackgroundHigh glucose (HG) is linked to dopaminergic neuron loss and related Parkinson’s disease (PD), but the mechanism is unclear.ResultsRats 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.ConclusionsHG induces dopaminergic neuronal apoptotic death via the Fyn/mTOR/S6K pathway.

Highlights

High glucose (HG) is linked to dopaminergic neuron loss and related Parkinson’s disease (PD), but the mechanism is unclear
An HG diet elevates cleaved caspase 3 levels and induces activation of Fyn and Mammalian target of rapamycin (mTOR)/S6 kinase (S6K) in the substantia nigra of rats Rats were divided into 2 groups: control and HG diet
Double labeled fluorescence staining suggested that Fyn and mTOR are localized in dopaminergic neurons in the substantia nigra (Fig. 1D)

Summary

Introduction

High glucose (HG) is linked to dopaminergic neuron loss and related Parkinson’s disease (PD), but the mechanism is unclear. Diabetes mellitus (DM) is associated with an increased risk for Parkinson’s disease (PD) [1, 2]. Dysregulated blood glucose levels have been identified as a risk marker for more rapid disease progression in PD [3]. The mechanism whereby this occurs is unclear. Experimental studies have suggested that neuronal apoptosis activation [4, 5] may play a crucial role in dopaminergic neuronal loss in the substantia nigra [6]. High glucose (HG) can cause human SH-SY5Y cell apoptosis [8], and this cell line is frequently chosen for PD

Methods

Results

Discussion

Conclusion