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

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 el...

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Autores principales: Tan, Changhong, Liu, Xi, Zhang, Xiaoshuai, Peng, Wuxue, Wang, Hui, Zhou, Wen, Jiang, Jin, Mo, Lijuan, Chen, Yangmei, Chen, Lifen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642997/
https://www.ncbi.nlm.nih.gov/pubmed/34863087
http://dx.doi.org/10.1186/s12860-021-00398-y
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author Tan, Changhong
Liu, Xi
Zhang, Xiaoshuai
Peng, Wuxue
Wang, Hui
Zhou, Wen
Jiang, Jin
Mo, Lijuan
Chen, Yangmei
Chen, Lifen
author_facet Tan, Changhong
Liu, Xi
Zhang, Xiaoshuai
Peng, Wuxue
Wang, Hui
Zhou, Wen
Jiang, Jin
Mo, Lijuan
Chen, Yangmei
Chen, Lifen
author_sort Tan, Changhong
collection PubMed
description 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.
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spelling pubmed-86429972021-12-06 Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment Tan, Changhong Liu, Xi Zhang, Xiaoshuai Peng, Wuxue Wang, Hui Zhou, Wen Jiang, Jin Mo, Lijuan Chen, Yangmei Chen, Lifen BMC Mol Cell Biol Research 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. BioMed Central 2021-12-04 /pmc/articles/PMC8642997/ /pubmed/34863087 http://dx.doi.org/10.1186/s12860-021-00398-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Tan, Changhong
Liu, Xi
Zhang, Xiaoshuai
Peng, Wuxue
Wang, Hui
Zhou, Wen
Jiang, Jin
Mo, Lijuan
Chen, Yangmei
Chen, Lifen
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642997/
https://www.ncbi.nlm.nih.gov/pubmed/34863087
http://dx.doi.org/10.1186/s12860-021-00398-y
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