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

  • BMC Mol Cell Biol. 2021 Dec 4;22(1):58. doi: 10.1186/s12860-021-00398-y.
Changhong Tan   #  1 ,  Xi Liu   #  1 ,  Xiaoshuai Zhang  2 ,  Wuxue Peng  1 ,  Hui Wang  1 ,  Wen Zhou  1 ,  Jin Jiang  1 ,  Lijuan Mo  1 ,  Yangmei Chen  3 ,  Lifen Chen  4
Affiliations
  • 1. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
  • 2. Chongqing Medical University, Chongqing, 400010, China.
  • 3. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China. [email protected].
  • 4. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China. [email protected].
  • # Contributed equally.
PMID: 34863087 DOI: 10.1186/s12860-021-00398-y
Abstract

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.

Keywords
Dopaminergic neuronal apoptosis; Fyn; High glucose; Parkinson’s disease; mTOR.
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