The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma.
To test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity.
Chung
S H
SH
College of Pharmacy, Seoul National University, South Korea.
Chung
S M
SM
Lee
J Y
JY
Kim
S R
SR
Park
K S
KS
Chung
J H
JH
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D010949:Plasma; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood / Q000378:metabolism*; D014812:Vitamin K / Q000378:metabolism* / Q000633:toxicity
D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014812:Vitamin K