19268528 |
de Lamirande E, Lamothe G, Villemure M: Control of superoxide and nitric oxide formation during human sperm capacitation. Free Radic Biol Med. 2009 May 15;46(10):1420-7. Epub 2009 Mar 4. We studied the modulation of superoxide anion (O (2).(-)) and nitric oxide (NO.) generation during human sperm capacitation (changes needed for the acquisition of fertility). The production of NO. (diaminofluorescein-2 fluorescence assay), but not that of O (2).(-) (luminescence assay), related to sperm capacitation was blocked by inhibitors of protein kinase C, Akt, protein tyrosine kinase, etc., but not by those of protein kinase A. Extracellular calcium (Ca (2+)) controlled O (2).(-) synthesis but extra- and intracellular Ca (2+) regulated NO. formation. Zinc inhibited capacitation and formation of O (2).(-) and NO.. Zinc chelators (TPEN and EDTA) and sulfhydryl-targeted compounds (diamide and N-ethylmaleimide) stimulated capacitation and formation of O (2).(-) and NO.; superoxide dismutase (SOD) and nitric oxide synthase inhibitor (L-NMMA) prevented these events. Diphenyliodonium (flavoenzyme inhibitor) blocked capacitation and related O (2).(-) synthesis but promoted NO. formation, an effect canceled by SOD and L-NMMA. NADPH induced capacitation and NO. (but not O (2).(-)) synthesis and these events were blocked by L-NMMA and not by SOD. Integration of these data on O (2).(-) and NO. production during capacitation reinforces the concept that a complex, but flexible, network of factors is involved and probably is associated with rescue mechanisms, so that spermatozoa can achieve successful fertilization. |
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