Effect of alkylating and redox cycling quinones on insulin receptor autophosphorylation.
Autophosphorylation is thought to be an essential step in the insulin receptor signal transduction cascade. Previous studies have shown that thiol alkylation of the receptor can block this receptor autophosphorylation, whereas an oxidative environment can increase this process. Since the toxicity of quinones can be related to two mechanisms-redox cycling resulting in oxidative stress, and arylation of cellular nucleophilic groups-the effects of 1,4-naphthoquinone and menadione on insulin receptor autophosphorylation were investigated. The results show that these two quinones have a dual effect: lower concentrations leading to oxidative stress increase insulin receptor autophosphorylation, whereas higher concentrations cause a thiol depletion and inhibit the normal insulin receptor autophosphorylation.
Van den Dobbelsteen
D J
DJ
Research Institute of Toxicology (RITOX), Utrecht University, PO Box 80.176, 3508 TD Utrecht, The Netherlands.
Toxopeus
C
C
van Holsteijn
C W
CW
Nooy
H A
HA
Droog
C I
CI
Horbach
G J
GJ
Noordhoek
J
J
Blaauboer
B J
BJ