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Recombinant long-glucocorticoid-induced leucine zipper (L-GILZ) protein restores the control of proliferation in gilz KO spermatogonia

Venanzi, Alessandra and Di Sante, Moises and Bruscoli, Stefano and Biagioli, Michele and Sorcini, Daniele and Cimino, Monica and Frammartino, Tiziana and Bereshchenko, Oxana and Franconi, Flavia and Riccardi, Claudio (2014) Recombinant long-glucocorticoid-induced leucine zipper (L-GILZ) protein restores the control of proliferation in gilz KO spermatogonia. European Journal of Pharmaceutical Sciences, Vol. 63 , p. 22-28. ISSN 0928-0987. eISSN 1879-0720. Article.

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DOI: 10.1016/j.ejps.2014.06.013

Abstract

No genes are yet directly implicated in etiology of male infertility. Identification of genes critical at various stages of spermatogenesis is pivotal for the timely diagnostic and treatment of infertility. We previously found that L-GILZ deficiency in a mouse KO model leads to hyperactivation of Ras signaling and increased proliferation in spermatogonia, resulting in male sterility.
The possibility to establish culture cell system that maintains spermatogonial cells in vitro allowed us to delivery a recombinant protein TAT-L-GILZ able to restore normal proliferation rate in gilz KO spermatogonia. We also found that N-terminal part of L-GILZ protein is responsible for Ras/L-GILZ protein-to-protein interaction, important for the control of proliferation rate of spermatogonia. Therefore, treatments increasing L-GILZ expression, such as delivering small molecules or peptides that mimic L-GILZ functions, are approaches with great potential of applicability for new therapeutic strategies based on gene/protein delivery to the affected testes.

Item Type:Article
ID Code:10805
Status:Published
Refereed:Yes
Uncontrolled Keywords:Glucocorticoid-induced leucine zipper, spermatogenesis, cell proliferation, Ras signaling
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Elsevier
ISSN:0928-0987
eISSN:1879-0720
Deposited On:18 Feb 2015 09:48

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