Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression in TM4 Sertoli cells.

ROSSI SP; REY-ARES V; FRUNGIERI MB; WINDSCHUETTL S; CALANDRA RS; MATZKIN ME; MAYERHOFER A

Saint Malo

Workshop; 19th European Testis Workshop; 2016

Testes are particularly vulnerable to oxidative stress. We previously described a PGD2 system in rodent Sertoli cells. Now, we found that PGD2 increases reactive oxygen species (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 PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant NAC and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide novel evidence for a role of PGD2 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 signaling pathway