Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function

Mark A. Baker, Anita Weinberg, Louise Hetherington, Ana-Izabel Villaverde, Tony Velkov, Jonathan Baell, Christopher P. Gordon

    Research output: Contribution to journalArticlepeer-review

    83 Citations (Scopus)

    Abstract

    Lipid peroxidation products such as the naturally occurring aldehyde 4-hydroxynonenal (4-HNE) are known to be cytotoxic toward different cell types, including spermatozoa. In order to understand this at the molecular level, we have employed a proteomic approach to characterize direct 4-HNE adducts on human spermatozoa. Several proteins were identified to be of particular interest, including aldehyde labeling of histone methyltransferase and dynein heavy chain. In addition, we found that 4-HNE bound to part of the activation segment, cysteine residue 199, of protein kinase A (PKA). Interestingly, at low levels, addition of 4-HNE had a stimulatory effect on PKA. However, this did not correlate to increased phosphotyrosine levels during capacitation. This data explains the link between reactive oxygen species and sperm toxicity. Given that epigenetic regulation is likely affected in oxidative-stressed spermatozoa, this data show that spermatozoa appear to shut down under these conditions before reaching the egg.
    Original languageEnglish
    Article number108
    Pages (from-to)1-10
    Number of pages10
    JournalBiology of Reproduction
    Volume92
    Issue number4
    DOIs
    Publication statusPublished - 2015

    Keywords

    • epigenetics
    • methyltransferases
    • protein kinases
    • proteomics

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