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Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells
The rapid and efficient clearance of apoptotic germ cells (GCs) by Sertoli cells (SCs) is important for spermatogenesis. High mitochondrial activity in phagocytes is critical for continued clearance of apoptotic cells. However, the underlying molecular mechanism is poorly understood. Glycogen syntha...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286816/ https://www.ncbi.nlm.nih.gov/pubmed/30398976 http://dx.doi.org/10.18632/aging.101614 |
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author | Gong, Yabin Zhang, Zhilong Chang, Zhanglin Zhou, Hao Zhao, Ruqian He, Bin |
author_facet | Gong, Yabin Zhang, Zhilong Chang, Zhanglin Zhou, Hao Zhao, Ruqian He, Bin |
author_sort | Gong, Yabin |
collection | PubMed |
description | The rapid and efficient clearance of apoptotic germ cells (GCs) by Sertoli cells (SCs) is important for spermatogenesis. High mitochondrial activity in phagocytes is critical for continued clearance of apoptotic cells. However, the underlying molecular mechanism is poorly understood. Glycogen synthase kinase-3α (GSK3α) is a protein kinase that participates in the regulation of mitochondrial activity. Immunohistochemistry evidenced the predominant presence of the Ser21 phosphorylation GSK3α (inactivation) signal in SCs. Heat shock-induced apoptosis of GCs and dephosphorylation of GSK3α in SCs is a perfect model to investigate the role of GSK3α in phagocytic action. The number of apoptotic GCs was significantly lower in GSK3α inhibitor pre-treated mice with HS compared to normal control. In vitro phagocytosis assays shown that the phagocytic activity in GSK3α activated SCs was downregulated, while GSK3α inhibitor supplementation restored this process. Moreover, GSK3α activation participates in the alteration of the mitochondrial ultrastructure and activity. In particular, GSK3α activation inhibits mitochondrial fission via phosphorylation of dynamin related protein 1 at Ser637. Changes of mitochondrial activity resulted in the accumulation of lipid droplets and the alteration of metabolism pattern in SCs. In summary, our results demonstrate that inactivation of GSK3α is required for mitochondria-mediated apoptotic GCs phagocytosis in SCs. |
format | Online Article Text |
id | pubmed-6286816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-62868162018-12-17 Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells Gong, Yabin Zhang, Zhilong Chang, Zhanglin Zhou, Hao Zhao, Ruqian He, Bin Aging (Albany NY) Research Paper The rapid and efficient clearance of apoptotic germ cells (GCs) by Sertoli cells (SCs) is important for spermatogenesis. High mitochondrial activity in phagocytes is critical for continued clearance of apoptotic cells. However, the underlying molecular mechanism is poorly understood. Glycogen synthase kinase-3α (GSK3α) is a protein kinase that participates in the regulation of mitochondrial activity. Immunohistochemistry evidenced the predominant presence of the Ser21 phosphorylation GSK3α (inactivation) signal in SCs. Heat shock-induced apoptosis of GCs and dephosphorylation of GSK3α in SCs is a perfect model to investigate the role of GSK3α in phagocytic action. The number of apoptotic GCs was significantly lower in GSK3α inhibitor pre-treated mice with HS compared to normal control. In vitro phagocytosis assays shown that the phagocytic activity in GSK3α activated SCs was downregulated, while GSK3α inhibitor supplementation restored this process. Moreover, GSK3α activation participates in the alteration of the mitochondrial ultrastructure and activity. In particular, GSK3α activation inhibits mitochondrial fission via phosphorylation of dynamin related protein 1 at Ser637. Changes of mitochondrial activity resulted in the accumulation of lipid droplets and the alteration of metabolism pattern in SCs. In summary, our results demonstrate that inactivation of GSK3α is required for mitochondria-mediated apoptotic GCs phagocytosis in SCs. Impact Journals 2018-11-06 /pmc/articles/PMC6286816/ /pubmed/30398976 http://dx.doi.org/10.18632/aging.101614 Text en Copyright © 2018 Gong et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Gong, Yabin Zhang, Zhilong Chang, Zhanglin Zhou, Hao Zhao, Ruqian He, Bin Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title | Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title_full | Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title_fullStr | Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title_full_unstemmed | Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title_short | Inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in Sertoli cells |
title_sort | inactivation of glycogen synthase kinase-3α is required for mitochondria-mediated apoptotic germ cell phagocytosis in sertoli cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286816/ https://www.ncbi.nlm.nih.gov/pubmed/30398976 http://dx.doi.org/10.18632/aging.101614 |
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