scholarly journals OGG1 protects mouse spermatogonial stem cells from reactive oxygen species in culture†

Author(s):  
Yoshifumi Mori ◽  
Narumi Ogonuki ◽  
Ayumi Hasegawa ◽  
Mito Kanatsu-Shinohara ◽  
Atsuo Ogura ◽  
...  

Abstract Although reactive oxygen species (ROS) are required for spermatogonial stem cell (SSC) self-renewal, they induce DNA damage and are harmful to SSCs. However, little is known about how SSCs protect their genome during self-renewal. Here, we report that Ogg1 is essential for SSC protection against ROS. While cultured SSCs exhibited homologous recombination-based DNA double-strand break repair at levels comparable with those in pluripotent stem cells, they were significantly more resistant to hydrogen peroxide than pluripotent stem cells or mouse embryonic fibroblasts, suggesting that they exhibit high levels of base excision repair (BER) activity. Consistent with this observation, cultured SSCs showed significantly lower levels of point mutations than somatic cells, and showed strong expression of BER-related genes. Functional screening revealed that Ogg1 depletion significantly impairs survival of cultured SSCs upon hydrogen peroxide exposure. Thus, our results suggest increased expression of BER-related genes, including Ogg1, protects SSCs from ROS-induced damage.

2014 ◽  
Vol 26 (7) ◽  
pp. 1500-1505 ◽  
Author(s):  
Zengguang Xu ◽  
Lei Zhang ◽  
Xuejie Fei ◽  
Xiuwen Yi ◽  
Wenxian Li ◽  
...  

2015 ◽  
Vol 31 (6) ◽  
pp. 279-286 ◽  
Author(s):  
Shigeo Saito ◽  
Ying-Chu Lin ◽  
Ming-Ho Tsai ◽  
Chang-Shen Lin ◽  
Yoshinobu Murayama ◽  
...  

Stem Cells ◽  
2016 ◽  
Vol 35 (1) ◽  
pp. 197-206 ◽  
Author(s):  
Roger E. Rönn ◽  
Carolina Guibentif ◽  
Shobhit Saxena ◽  
Niels-Bjarne Woods

2015 ◽  
Vol 87 ◽  
pp. S117
Author(s):  
Olga G. Lyublinskaya ◽  
Irina S. Smirnova ◽  
Natalia A. Pugovkina ◽  
Valeriy V. Zenin ◽  
Nikolay N. Nikolsky

Stem Cells ◽  
2021 ◽  
Author(s):  
Julia S. Ivanova ◽  
Natalia A. Pugovkina ◽  
Irina E. Neganova ◽  
Irina V. Kozhukharova ◽  
Nikolay N. Nikolsky ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Bin Zhao ◽  
Jie Luo ◽  
Ye Wang ◽  
Liangfu Zhou ◽  
Jingmin Che ◽  
...  

Osteosarcoma is the most frequently diagnosed primary malignant bone sarcoma in children and adolescents. Recent studies have shown that cancer stem cells (CSCs), a cluster of tumor cells with the ability to self-renew, play an essential role in tumor recurrence and metastasis. Thus, it is necessary to develop therapeutic strategies specifically targeting CSCs. Metformin, the first-line drug for type 2 diabetes, exhibits antineoplastic activities in various kinds of tumors. New evidence has suggested that metformin may target CSCs and prevent their recurrence. However, the underlying specific mechanisms remain unclear. In this study, we found that metformin significantly suppressed the self-renewal ability of osteosarcoma stem cells (OSCs) and induced G0/G1 phase arrest by blocking the activity of cyclin-dependent kinases. Furthermore, metformin induced apoptosis through a mitochondria-dependent pathway, leading to the collapse of the mitochondrial transmembrane potential and the production of reactive oxygen species (ROS). Importantly, metformin acted directly on the mitochondria, which resulted in decreased ATP synthesis. This change allowed access to the downstream AMPK kinase, and the activation of AMPK led to the reversal of the mTOR pathway, triggering autophagy. Particularly, metformin-mediated autophagy disturbed the homeostasis of stemness and pluripotency in the OSCs. Additionally, our mouse xenograft model confirmed the potential therapeutic use of metformin in targeting OSCs. In conclusion, our findings suggest that metformin suppresses the self-renewal ability and tumorigenicity of OSCs via ROS-mediated apoptosis and autophagy.


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