Thrombin induces S-D-lactoylglutathione accumulation by enhancing platelet glycolytic pathway.
1. Thrombin addition to human platelets stimulates L(+)lactate formation and S-D-lactoylglutathione (SDL) accumulation. 2. Monoiodoacetamide decreases lactate formation and potentiates SDL accumulation through a significant increase of dihydroxyacetone phosphate and fructose1,6bisphosphate intracellular levels both in resting and in activated platelets. 3. A similar effect is produced by exogenous methylglyoxal on L(+)lactate formation and SDL accumulation. 4. Resting platelets completely transform (1 hr at 37 degrees C) the ketoaldehyde into D(-)lactate: 5. When platelets are incubated in the presence of thrombin only 60% of the ketoaldehyde is found as D(-)lactate and the accumulated S-D-lactoylglutathione represents about the 0.7% of the initial substrate. 6. During platelet stimulation with thrombin the hemithioacetal adduct, formed as a by-product of glycolytic pathway, can be rapidly removed for important steps of cellular activation.
Leoncini
G
G
Istituto Policattedra di Chimica Biologica, Universitá di Genova, Italy.
Buzzi
E
E
D000478:Alkylation; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007460:Iodoacetamide / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D011765:Pyruvaldehyde / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D007773:Lactates; D019344:Lactic Acid; D011765:Pyruvaldehyde; D013917:Thrombin; D005978:Glutathione; C013585:S-lactoylglutathione; D007460:Iodoacetamide