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Publication : Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling pathway.

First Author  Shen X Year  2018
Journal  Int J Mol Med Volume  42
Issue  5 Pages  2819-2830
PubMed ID  30106128 Mgi Jnum  J:329583
Mgi Id  MGI:6881436 Doi  10.3892/ijmm.2018.3825
Citation  Shen X, et al. (2018) Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling pathway. Int J Mol Med 42(5):2819-2830
abstractText  Stimulated by retinoic acid 8 (Stra8), one of genes induced by retinoic acid (RA), is required for the meiotic initiation of male spermatogenesis. The present study found that Stra8 inhibited apoptosis in male Stra8knockout mice, and in mice with vitamin A deficiency and vitamin A recovery in vivo. This phenotype was also verified in GC1 spermatogonia (spg) cells overexpressing Stra8. In addition, microarray analysis identified that there were nine differentially expressed genes (DEGs) in the Stra8overexpressed GC1 spg cells compared with the control groups; the expression of these nine genes was verified via mRNA expression levels. The DEGs were as follows: Phosphatidylinositoldependent kinase 1 (PDK1), a key gene upstream of protein kinase B (AKT); angiopoietin 2, a Bcell lymphoma 2 (Bcl2)inhibited gene; transcription factor 4, glutathione Stransferase P91 and ubiquitinspecific protease 33, mitogenactivated protein kinase (MAPK)related genes; oxidative stress induced growth inhibitor 1, related to the P53 pathway; Bcl2, P53, ERK (MAPK1/3), cJun Nterminal kinase (MAPK8/9), and P38 (MAPK14), all of which are key genes involved in the AKT signaling pathway. Therefore, the present study further verified these genes and found that the mRNA and protein expression levels of PDK1, AKT, Bcl2 and ERK were increased. Although the mRNA expression level of P53 was decreased, there was no significant difference in the protein expression level in Stra8overexpressing GC1 spg cells compared with controls. In addition, Caspase 3, one of the executioner caspases, was decreased in Stra8overexpressing GC1 spg cells compared with the control groups. Therefore, it was suggested that Stra8 may directly or indirectly inhibit caspases through the AKT signaling pathway and ultimately exert an antiapoptotic effect in the male reproductive system.
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