TY - JOUR
T1 - Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function
AU - Baker, Mark A.
AU - Weinberg, Anita
AU - Hetherington, Louise
AU - Villaverde, Ana-Izabel
AU - Velkov, Tony
AU - Baell, Jonathan
AU - Gordon, Christopher P.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - epigenetics
KW - methyltransferases
KW - protein kinases
KW - proteomics
UR - http://handle.uws.edu.au:8081/1959.7/uws:30374
U2 - 10.1095/biolreprod.114.126680
DO - 10.1095/biolreprod.114.126680
M3 - Article
SN - 1529-7268
SN - 0006-3363
VL - 92
SP - 1
EP - 10
JO - Biology of Reproduction
JF - Biology of Reproduction
IS - 4
M1 - 108
ER -