Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells
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...
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| Published in: | Molecular and cellular endocrinology Vol. 434; pp. 154 - 165 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier B.V
15-10-2016
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| Abstract | 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.
•PGD2 is a local modulator of the oxidant/antioxidant status in Sertoli cells.•PGD2 is a stimulatory factor of ROS and H2O2 production in Sertoli cells.•ROS/H2O2 are mediators of PGD2 effect on LDH expression/activity in Sertoli cells.•PGD2 up-regulates LDH expression/activity via DP1/DP2 receptors in Sertoli cells.•ROS and the Akt-CREB/ATF-1 pathway are proposed to partake in PGD2 action on LDH. |
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| AbstractList | 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. 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. •PGD2 is a local modulator of the oxidant/antioxidant status in Sertoli cells.•PGD2 is a stimulatory factor of ROS and H2O2 production in Sertoli cells.•ROS/H2O2 are mediators of PGD2 effect on LDH expression/activity in Sertoli cells.•PGD2 up-regulates LDH expression/activity via DP1/DP2 receptors in Sertoli cells.•ROS and the Akt-CREB/ATF-1 pathway are proposed to partake in PGD2 action on LDH. |
| Author | Rey-Ares, Verónica Windschüttl, Stefanie Matzkin, María E. Ponzio, Roberto Terradas, Claudio Puigdomenech, Elisa Levalle, Oscar Rossi, Soledad P. Frungieri, Mónica B. Calandra, Ricardo S. Mayerhofer, Artur |
| Author_xml | – sequence: 1 givenname: Soledad P. surname: Rossi fullname: Rossi, Soledad P. email: soledadrossi3@hotmail.com organization: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina – sequence: 2 givenname: Stefanie surname: Windschüttl fullname: Windschüttl, Stefanie organization: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany – sequence: 3 givenname: María E. surname: Matzkin fullname: Matzkin, María E. organization: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina – sequence: 4 givenname: Verónica surname: Rey-Ares fullname: Rey-Ares, Verónica organization: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany – sequence: 5 givenname: Claudio surname: Terradas fullname: Terradas, Claudio organization: División Endocrinología, Hospital Durand, Facultad de Medicina, Universidad de Buenos Aires, Díaz Vélez 5044, 1405, Ciudad de Buenos Aires, Argentina – sequence: 6 givenname: Roberto surname: Ponzio fullname: Ponzio, Roberto organization: Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Ciudad de Buenos Aires, Argentina – sequence: 7 givenname: Elisa surname: Puigdomenech fullname: Puigdomenech, Elisa organization: Instituto Médico PREFER, Güemes 2348, 1650, San Martín, Provincia de Buenos Aires, Argentina – sequence: 8 givenname: Oscar orcidid: 0000-0003-4780-9045 surname: Levalle fullname: Levalle, Oscar organization: División Endocrinología, Hospital Durand, Facultad de Medicina, Universidad de Buenos Aires, Díaz Vélez 5044, 1405, Ciudad de Buenos Aires, Argentina – sequence: 9 givenname: Ricardo S. surname: Calandra fullname: Calandra, Ricardo S. organization: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina – sequence: 10 givenname: Artur surname: Mayerhofer fullname: Mayerhofer, Artur organization: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany – sequence: 11 givenname: Mónica B. surname: Frungieri fullname: Frungieri, Mónica B. organization: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina |
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| Keywords | Testis PGD2 Pxr1 Reactive oxygen species H2O2 CLU Gpx LDH CREB PI3K H-PGDS COX2 SOX9 AMH PGs Sertoli cell PDHA1 L-PGDS Lactate dehydrogenase Prostaglandin D2 Sod1 NR5A1 AR NAC GDNF Cat CRE ROS SHBG SCO Prostaglandin D HO |
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| SubjectTerms | Adult Animals Cell Line DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation - drug effects H2O2 Humans Hydrogen Peroxide - metabolism Lactate dehydrogenase Lactate Dehydrogenases - metabolism Male Mice Prostaglandin D2 Prostaglandin D2 - pharmacology Reactive oxygen species Reactive Oxygen Species - metabolism Sertoli cell Sertoli Cells - drug effects Sertoli Cells - metabolism Signal Transduction - drug effects Testis Transcription Factor DP1 - genetics Transcription Factor DP1 - metabolism Transcription Factors - genetics Transcription Factors - metabolism |
| Title | Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells |
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