title: Sphingosine-1-phosphate in inhibition of male germ cell apoptosis in the human testis.
abstract: It has been suggested that apoptosis is controlled by two intracellular sphingolipids, ceramide and sphingosine-1-phosphate (S1P), which are widely distributed in mammalian tissues. In the ovary, S1P was found to effectively block apoptosis caused by cancer therapies. Its role in male germ cell death, however, was unknown. In this study, we investigated the effects of ceramide and S1P on human male germ cell apoptosis. Germ cell death was induced by incubation of segments of seminiferous tubules in vitro. During apoptosis, ceramide levels increased rapidly before appearance of caspase 3 activation and DNA laddering, suggesting a role for ceramide in the induction of germ cell death. Ceramide appeared to regulate an early step of apoptosis because n-acetyl-L-cysteine and blockade of mitochondrial respiration inhibited apoptosis but had no effect on ceramide levels. Moreover, fumonisin B1 (ceramide synthetase inhibitor) did not significantly affect testicular apoptosis. Therefore, elevated ceramide levels are likely to result from breakdown of sphingomyelin rather than from de novo synthesis. Finally, we found that S1P at 1 and 10 micromol/liter suppressed germ cell apoptosis by 30% (P < 0.001). Taken together, sphingolipids appear to play a role in male germ cell apoptosis and can partly be inhibited by S1P.
authors: Programme for Developmental and Reproductive Biology, Biomedicum Helsinki, and Hospital for Children and Adolescents, University of Helsinki, FIN-00029 Helsinki, Finland. laura.suomalainen@hus.fi
authors: Laura
authors: L
authors: Suomalainen
authors: Jukka K
authors: JK
authors: Hakala
authors: Virve
authors: V
authors: Pentikäinen
authors: Marjut
authors: M
authors: Otala
authors: Krista
authors: K
authors: Erkkilä
authors: Markku O
authors: MO
authors: Pentikäinen
authors: Leo
authors: L
authors: Dunkel
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037341:Fumonisins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008246:Lysophospholipids; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011190:Potassium Cyanide / Q000494:pharmacology; D012671:Seminiferous Tubules / Q000166:cytology; D013090:Spermatocytes / Q000166:cytology* / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D002518:Ceramides; D004791:Enzyme Inhibitors; D037341:Fumonisins; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; C056933:fumonisin B1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase; D011190:Potassium Cyanide; D013110:Sphingosine