title: Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction.
abstract: Bacterial lipopolysaccharide (LPS) is the most important contributing factor in pathogenesis of bacterial infection in male accessory glands; and it has shown to inhibit testicular steroidogenesis and induce apoptosis. The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis. LC-540 Leydig cells treated with LPS (10 µg/ml) showed impaired steroidogenesis and increased cellular apoptosis. The mRNA and protein expression of SIRT4 were decreased in LPS treated cells when compared to controls. The obtained data suggest that the c-Jun N-terminal kinase (JNK) activation suppresses SIRT4 expression in LPS treated Leydig cells. Furthermore, the overexpression of SIRT4 prevented LPS induced impaired steroidogenesis and cellular apoptosis by improving mitochondrial function. These findings provide valuable information that SIRT4 regulates LPS mediated Leydig cell dysfunction.
authors.affiliation: Department of Biochemistry, Bharathidasan University, Tiruchirappalli, India.
authors.forename: Balamurugan
authors.initials: B
authors.lastname: Ramatchandirin
authors.affiliation: Department of Biochemistry, Bharathidasan University, Tiruchirappalli, India.
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Sadasivam
authors.affiliation: Department of Biochemistry, Bharathidasan University, Tiruchirappalli, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Kannan
authors.affiliation: Department of Biochemistry, Bharathidasan University, Tiruchirappalli, India.
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Prahalathan
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D005978:Glutathione / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013267:Stilbenes; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases; C530376:SIRT5 protein, rat; D037761:Sirtuins; D005978:Glutathione; D000077185:Resveratrol
keywords: APOPTOSIS; LEYDIG CELLS; LPS; SIRT4; STEROIDOGENESIS