(S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.
α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.
Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Shanghai, China.
Hao
H
Zhang
Huan
H
Yu
Xia
X
Wang
Weiwei
W
Zheng
Bei
B
Yang
Jingbo
J
Pi
Gengsheng
G
He
Weidong
W
Qu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D010766:Phosphorylation / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D000517:alpha-Chlorohydrin / Q000494:pharmacology*
D014443:Tyrosine; D000255:Adenosine Triphosphate; D000517:alpha-Chlorohydrin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases