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SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging

Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endom...

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Autores principales: Lan, Yong, Dong, Min, Li, Yongjun, Diao, Yongpeng, Chen, Zuoguang, Li, Yangfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920857/
https://www.ncbi.nlm.nih.gov/pubmed/33717652
http://dx.doi.org/10.1016/j.omtn.2021.01.023
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author Lan, Yong
Dong, Min
Li, Yongjun
Diao, Yongpeng
Chen, Zuoguang
Li, Yangfang
author_facet Lan, Yong
Dong, Min
Li, Yongjun
Diao, Yongpeng
Chen, Zuoguang
Li, Yangfang
author_sort Lan, Yong
collection PubMed
description Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.
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spelling pubmed-79208572021-03-12 SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging Lan, Yong Dong, Min Li, Yongjun Diao, Yongpeng Chen, Zuoguang Li, Yangfang Mol Ther Nucleic Acids Original Article Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging. American Society of Gene & Cell Therapy 2021-01-26 /pmc/articles/PMC7920857/ /pubmed/33717652 http://dx.doi.org/10.1016/j.omtn.2021.01.023 Text en © 2021. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Lan, Yong
Dong, Min
Li, Yongjun
Diao, Yongpeng
Chen, Zuoguang
Li, Yangfang
SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title_full SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title_fullStr SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title_full_unstemmed SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title_short SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging
title_sort sirt1-induced deacetylation of akt expedites platelet phagocytosis and delays hemec aging
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920857/
https://www.ncbi.nlm.nih.gov/pubmed/33717652
http://dx.doi.org/10.1016/j.omtn.2021.01.023
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