Effect of GSH depletion by 1-chloro-2,4-dinitrobenzene on human platelet aggregation, arachidonic acid oxidative metabolism and cytoskeletal proteins.
Platelet reduced glutathione (GSH) is completely depleted by 1-chloro-2,4-dinitrobenzene (CDNB), which is a substrate for GSH-S-transferase. GSH-depleted platelets: a) aggregate normally at high inducer concentration; b) respond with increased (after arachidonic acid) or depressed (after collagen) aggregability at low inducer concentration; c) show almost no arachidonic acid-induced stimulation of the hexose monophosphate shunt; d) are sensitized to oxidant agents such as diamide, which elicits a faster cytoskeletal protein oxidative polymerization and reversible aggregation. Our results suggest that GSH acts as a reducing cofactor and/or free radical scavenger in the PG-hydroperoxidase step of the cyclooxygenase pathway; moreover, GSH protects membrane and cytoskeletal protein -SH groups from oxidation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood*; D009578:Nitrobenzenes / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*
D001095:Arachidonic Acids; D004137:Dinitrochlorobenzene; D008840:Microfilament Proteins; D009578:Nitrobenzenes; D016718:Arachidonic Acid; D003094:Collagen; D005978:Glutathione