Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment
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...
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2021
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oai:doaj.org-article:07db3d4d479a4271b34493c9b0bb7ad82021-12-05T12:17:30ZFyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment10.1186/s12860-021-00398-y2661-8850https://doaj.org/article/07db3d4d479a4271b34493c9b0bb7ad82021-12-01T00:00:00Zhttps://doi.org/10.1186/s12860-021-00398-yhttps://doaj.org/toc/2661-8850Abstract 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.Changhong TanXi LiuXiaoshuai ZhangWuxue PengHui WangWen ZhouJin JiangLijuan MoYangmei ChenLifen ChenBMCarticleHigh glucoseDopaminergic neuronal apoptosisParkinson’s diseaseFynmTORCytologyQH573-671ENBMC Molecular and Cell Biology, Vol 22, Iss 1, Pp 1-11 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
High glucose Dopaminergic neuronal apoptosis Parkinson’s disease Fyn mTOR Cytology QH573-671 |
| spellingShingle |
High glucose Dopaminergic neuronal apoptosis Parkinson’s disease Fyn mTOR Cytology QH573-671 Changhong Tan Xi Liu Xiaoshuai Zhang Wuxue Peng Hui Wang Wen Zhou Jin Jiang Lijuan Mo Yangmei Chen Lifen Chen Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| description |
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. |
| format |
article |
| author |
Changhong Tan Xi Liu Xiaoshuai Zhang Wuxue Peng Hui Wang Wen Zhou Jin Jiang Lijuan Mo Yangmei Chen Lifen Chen |
| author_facet |
Changhong Tan Xi Liu Xiaoshuai Zhang Wuxue Peng Hui Wang Wen Zhou Jin Jiang Lijuan Mo Yangmei Chen Lifen Chen |
| author_sort |
Changhong Tan |
| title |
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| title_short |
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| title_full |
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| title_fullStr |
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| title_full_unstemmed |
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment |
| title_sort |
fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (hg) treatment |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/07db3d4d479a4271b34493c9b0bb7ad8 |
| work_keys_str_mv |
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