title: Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function.
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.
authors: Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, Callaghan, Australia Mark.Baker@newcastle.edu.au.
authors: Mark A
authors: MA
authors: Baker
authors: Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, Callaghan, Australia.
authors: Anita
authors: A
authors: Weinberg
authors: Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, Callaghan, Australia.
authors: Louise
authors: L
authors: Hetherington
authors: Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, Callaghan, Australia.
authors: Ana-Izabel
authors: AI
authors: Villaverde
authors: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors: Tony
authors: T
authors: Velkov
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors: Jonathan
authors: J
authors: Baell
authors: Nanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Penrith New South Wales, Australia.
authors: Christopher P
authors: CP
authors: Gordon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000447:Aldehydes / Q000633:toxicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013075:Sperm Capacitation / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; D019000:Phosphotyrosine; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D004398:Dyneins; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxynonenal; epigenetics; methyltransferase; protein kinase; proteomics