PMID- 26189884 OWN - NLM STAT- MEDLINE DCOM- 20160422 LR - 20151023 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 231 IP - 2 DP - 2016 Feb TI - D-Aspartate Induces Proliferative Pathways in Spermatogonial GC-1 Cells. PG - 490-5 LID - 10.1002/jcp.25095 [doi] AB - D-aspartate (D-Asp) is an endogenous amino acid present in vertebrate tissues, with particularly high levels in the testis. In vivo studies indicate that D-Asp indirectly stimulates spermatogenesis through the hypothalamic-pituitary-gonadal axis. Moreover, in vitro studies have demonstrated that D-Asp up-regulates testosterone production in Leydig cells by enhancing expression of the steroidogenic acute regulatory protein. In this study, a cell line derived from immortalized type-B mouse spermatogonia retaining markers of mitotic germ cells (GC-1) was employed to explore more direct involvement of D-Asp in spermatogenesis. Activity and protein expression of markers of cell proliferation were determined at intervals during incubation in D-Asp-containing medium. D-Asp induced phosphorylation of ERK and Akt proteins, stimulated expression of PCNA and Aurora B, and enhanced mRNA synthesis and protein expression of P450 aromatase and protein expression of Estrogen Receptor beta (ERbeta). These results are the first demonstration of a direct effect of D-Asp on spermatogonial mitotic activity. Considering that spermatogonia express the NR1 subunit of the N-Methyl-D-Aspartic Acid receptor (NMDAR), we suggest that their response to D-Asp depends on NMDAR-mediated activation of the ERK and Akt pathways and is further enhanced by activation of the P450 aromatase/ERbeta pathway. CI - (c) 2015 Wiley Periodicals, Inc. FAU - Santillo, Alessandra AU - Santillo A AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy. FAU - Falvo, Sara AU - Falvo S AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy. FAU - Chieffi, Paolo AU - Chieffi P AD - Dipartimento di Psicologia, Seconda Universita di Napoli, Caserta, Italy. FAU - Di Fiore, Maria Maddalena AU - Di Fiore MM AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy. FAU - Senese, Rosalba AU - Senese R AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy. FAU - Chieffi Baccari, Gabriella AU - Chieffi Baccari G AD - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Universita di Napoli, Caserta, Italy. LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Proliferating Cell Nuclear Antigen) RN - 0 (RNA, Messenger) RN - 4SR0Q8YD1X (D-Aspartic Acid) RN - EC 1.14.14.1 (Aromatase) RN - EC 2.7.11.1 (Aurkb protein, mouse) RN - EC 2.7.11.1 (Aurora Kinase B) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Aromatase/genetics/metabolism MH - Aurora Kinase B/metabolism MH - Cell Line MH - Cell Proliferation/drug effects/genetics/physiology MH - D-Aspartic Acid/*metabolism/*pharmacology MH - MAP Kinase Signaling System MH - Male MH - Mice MH - Models, Biological MH - Proliferating Cell Nuclear Antigen/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics/metabolism MH - Signal Transduction/drug effects MH - Spermatogenesis/*drug effects/genetics/*physiology MH - Spermatogonia/*cytology/*drug effects/metabolism EDAT- 2015/07/21 06:00 MHDA- 2016/04/23 06:00 CRDT- 2015/07/21 06:00 PHST- 2015/06/03 00:00 [received] PHST- 2015/07/17 00:00 [accepted] PHST- 2015/07/21 06:00 [entrez] PHST- 2015/07/21 06:00 [pubmed] PHST- 2016/04/23 06:00 [medline] AID - 10.1002/jcp.25095 [doi] PST - ppublish SO - J Cell Physiol. 2016 Feb;231(2):490-5. doi: 10.1002/jcp.25095.