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Rossi, Soledad P.; Windschüttl, Stefanie; Matzkin, Maria E.; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S.; Mayerhofer, Artur; Frungieri, Mónica B. (2016): Reactive oxygen species (ROS) production triggered by prostaglandin D-2 (PGD(2)) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells. In: Molecular and Cellular Endocrinology, Vol. 434, No. C: pp. 154-165
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Abstract

Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D-2 (PGD(2)) system in Sertoli cells. Now, we found that PGD(2) increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD(2) on lactate dehydrogenase (LDH) expression via DP1 /DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD(2) also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD(2) in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway. (C) 2016 ELSEVIER. All rights reserved.