Antithrombin activity is inhibited by acrolein and homocysteine thiolactone: Protection by cysteine

Life Sciences
Alejandro Gugliucci

Abstract

Conditions in which serum or tissue acrolein levels are high (e.g.: renal failure, heavy smoking, oxidative stress) are also associated with increased thrombogenicity. Another emerging cardiovascular risk factor is homocysteine, and its derivative, homocysteine thiolactone. Antithrombin is one of the most important inhibitors of blood coagulation Since its activation by heparin binding requires critical interactions involving 3 Lys residues; we hypothesized that acrolein or homocysteine thiolactone impair antithrombin activity. When we incubated human antithrombin with increasing concentrations of acrolein (0-2 mmol/L) over a short period of time (0-4 h), a time and concentration dependent loss of activity was apparent (IC(50)=0.25 mmol/L). At 2 mmol/L, maximum inhibition (60%) is achieved at 1 h. This loss of activity was mirrored by changes in the electrophoretic pattern (homogeneity of the native antithrombin band as well as polymerization). In the same conditions, homocysteine thiolactone produces a significant, yet far less pronounced effect; acrolein being 3 times more potent than homocysteine thiolactone. When antithrombin was co-incubated with acrolein and cysteine, only less than 10% of antithrombin activity was lost. ...Continue Reading

References

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Citations

Aug 2, 2011·Molecular Nutrition & Food Research·Giancarlo AldiniMarina Carini
Jun 30, 2011·Molecular Nutrition & Food Research·Qin ZhuMingfu Wang
Jun 25, 2013·Free Radical Biology & Medicine·Oren RomAbraham Z Reznick
May 23, 2012·Journal of Muscle Research and Cell Motility·Oren RomAbraham Z Reznick

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