E. Delamirande et C. Gagnon, PARADOXICAL EFFECT OF REAGENTS FOR SULFHYDRYL AND DISULFIDE GROUPS ONHUMAN SPERM CAPACITATION AND SUPEROXIDE PRODUCTION, Free radical biology & medicine, 25(7), 1998, pp. 803-817
Spermatozoa must undergo capacitation prior to fertilization. In human
s, this process appears regulated by oxidoreduction reactions. We inve
stigated the possibility that these reactions involved the sulfhydryl-
disulfide pair, which offers a reversible regulation of cellular proce
sses. The effects of reagents targeted for sulfhydryl and disulfide gr
oups on human sperm capacitation, superoxide (O-2(.-)) generation and
protein tyrosine phosphorylation were evaluated. The sulfhydryl target
ed agents, phenylarsine oxide (PAO), diamide, dithiopyridine (DTP), N-
ethylmaleimide ((NEM), maleimidylpropionyl biocytin (MPB), p-chloromer
curibenzoic acid (PCMB), and bromobimane analogs (mBBr and qBBr) trigg
ered sperm capacitation to levels comparable to those observed with a
biological inducer, fetal cord serum ultrafiltrate (FCSu). Capacitatio
n induced by NEM, MPB, PCMB, and PAO was prevented by superoxide dismu
tase (SOD) and associated with an increased sperm production of O2(.-)
. However, SOD did not affect the increase in protein tyrosine phospho
rylation of spermatozoa treated with NEM, PAO, or MPB. Disulfide reduc
tants, dithiothreitol (DTT), thioredoxin (TRX), glutathione (GSH), tri
s-(2-carboxyethyl) phosphine (TCEP), and tris-(2-cyanoethyl) phosphine
(TCP) partially to totally inhibited FCSu-induced sperm capacitation
and O2(.-) production. TCEP, DTT, and TRX decreased the capacitation-a
ssociated tyrosine phosphorylation of sperm proteins. The strong time-
dependent increase of sperm membrane sulfhydryl groups exposed to the
extracellular space occurring during the 'first hour of capacitation c
ould indicate an important rearrangement of sulfhydryl carrying protei
ns during the initiation of capacitation. Therefore, protein sulfhydry
l-disulfide status may be important for the regulation of human sperm
capacitation and the mechanisms involved may be complex and multifacto
rial. (C) 1998 Elsevier Science Inc.