NOX5 in human spermatozoa: Expression, function, and regulation

Boris Musset, Robert A. Clark, Thomas E. DeCoursey, Gabor L. Petheo, Miklos Geiszt, Yumin Chen, John E. Cornell, Carlton A. Eddy, Robert G. Brzyski, Amina El Jamali

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H 2O 2 exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca 2+ chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H 2O 2- induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the H V1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and H V1. H 2O 2 treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility.

Original languageEnglish (US)
Pages (from-to)9376-9388
Number of pages13
JournalJournal of Biological Chemistry
Volume287
Issue number12
DOIs
StatePublished - Mar 16 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Musset, B., Clark, R. A., DeCoursey, T. E., Petheo, G. L., Geiszt, M., Chen, Y., Cornell, J. E., Eddy, C. A., Brzyski, R. G., & El Jamali, A. (2012). NOX5 in human spermatozoa: Expression, function, and regulation. Journal of Biological Chemistry, 287(12), 9376-9388. https://doi.org/10.1074/jbc.M111.314955