title: Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.
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.
authors.affiliation: 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. Electronic address: soledadrossi3@hotmail.com.
authors.forename: Soledad P
authors.initials: SP
authors.lastname: Rossi
authors.affiliation: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Windschüttl
authors.affiliation: 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.
authors.forename: María E
authors.initials: ME
authors.lastname: Matzkin
authors.affiliation: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany.
authors.forename: Verónica
authors.initials: V
authors.lastname: Rey-Ares
authors.affiliation: División Endocrinología, Hospital Durand, Facultad de Medicina, Universidad de Buenos Aires, Díaz Vélez 5044, 1405, Ciudad de Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Terradas
authors.affiliation: Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Ciudad de Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ponzio
authors.affiliation: Instituto Médico PREFER, Güemes 2348, 1650, San Martín, Provincia de Buenos Aires, Argentina.
authors.forename: Elisa
authors.initials: E
authors.lastname: Puigdomenech
authors.affiliation: División Endocrinología, Hospital Durand, Facultad de Medicina, Universidad de Buenos Aires, Díaz Vélez 5044, 1405, Ciudad de Buenos Aires, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Levalle
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428, Ciudad de Buenos Aires, Argentina.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Calandra
authors.affiliation: BioMedizinisches Centrum (BMC), Ludwig-Maximilians-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152, Planegg, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
authors.affiliation: 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.
authors.forename: Mónica B
authors.initials: MB
authors.lastname: Frungieri
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000378:metabolism*; D008297:Male; D051379:Mice; D015230:Prostaglandin D2 / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050680:Transcription Factor DP1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; C493735:TFDP1 protein, human; C094103:TFDP2 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D045022:Lactate Dehydrogenases; D015230:Prostaglandin D2
keywords: H(2)O(2); Lactate dehydrogenase; Prostaglandin D(2); Reactive oxygen species; Sertoli cell; Testis