Open AccessDefining the Mechanisms by Which the Reactive Oxygen Species By-Product, 4-Hydroxynonenal, Affects Human Sperm Cell Function1
Author(s) -
Mark A. Baker,
Anita Weinberg,
Louise Hetherington,
Ana-Izabel Villaverde,
Tony Velkov,
Jonathan B. Baell,
Christopher P. Gordon
Publication year - 2015
Publication title -
biology of reproduction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.366
H-Index - 180
eISSN - 1529-7268
pISSN - 0006-3363
DOI - 10.1095/biolreprod.114.126680
Subject(s) - 4 hydroxynonenal , biology , reactive oxygen species , capacitation , lipid peroxidation , microbiology and biotechnology , sperm , biochemistry , oxidative stress , genetics
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