2. Academic Validation
  3. Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment

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

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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