Rossi Soledad P, Windschüttl Stefanie, Matzkin María E, Rey-Ares Verónica, Terradas Claudio, Ponzio Roberto, Puigdomenech Elisa, Levalle Oscar, Calandra Ricardo S, Mayerhofer Artur, Frungieri Mónica B
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Ciudad de Buenos Aires, Argentina.
BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany.
Mol Cell Endocrinol. 2016 Oct 15;434:154-65. doi: 10.1016/j.mce.2016.06.021. Epub 2016 Jun 18.
Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 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 PGD2 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. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide 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 pathway.
活性氧（ROS）在健康和疾病状态下调节睾丸功能。我们之前描述了支持细胞中的前列腺素D2（PGD2）系统。现在，我们发现PGD2可增加小鼠TM4支持细胞中ROS和过氧化氢（H2O2）的生成，还能诱导抗氧化酶的表达，这表明防御系统作为一种适应性应激机制被触发，以确保细胞存活。ROS特别是H2O2可能作为第二信使调节信号转导通路和基因表达。我们描述了PGD2通过DP1/DP2受体对乳酸脱氢酶（LDH）表达的刺激作用，抗氧化剂N-乙酰-L-半胱氨酸和PI3K/Akt通路抑制剂LY 294002可阻止这种作用。PGD2还可增强Akt和CREB/ATF-1的磷酸化。我们的结果为PGD2在支持细胞氧化/抗氧化状态调节中的作用提供了证据，更重要的是，为通过ROS生成和Akt-CREB/ATF-1通路调节LDH表达提供了证据。
