caa a22 4500 378881469 CHVBK 20180305123432.0 cr unu---uuuuu 161128e20030807xx s 000 0 eng 10.1515/CCLM.2003.164 doi (NATIONALLICENCE)gruyter-10.1515/CCLM.2003.164 Gugliucci Alejandro Human Plasminogen Is Highly Susceptible to Peroxynitrite Inactivation [Elektronische Daten] [Alejandro Gugliucci] It has been shown that diabetic patients have up to three-fold increases in plasma nitrated tyrosine. We hypothesize that nitration of plasminogen could impair its catalytic properties and be a factor in diabetic thrombogenicity. To test this hypothesis, in this study we addressed the effects of the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) on human streptokinase-induced plasmin activity. Given the link between glycation and oxidation we also explored whether peroxynitrite enhances the effect of fructose (1-5 mmol/l) and glucose (5-50 mmol/l) on plasminogen. We provide evidence that plasminogen, but not antithrombin III, is quickly inactivated by exogenously generated peroxynitrite (0-20 mmol/l SIN-1), in a timeand dose-dependent manner. The effect occurs even when the molar ratio of other plasma proteins and key antioxidants is respected. In our system, peroxynitrite did not enhance the effect of the sugars. Preincubation of the sugars with peroxynitrite also failed to produce any effect. This suggests that in conditions and times approaching the in vivo situation, plasminogen is more susceptible to peroxynitrite damage than to carbonyl damage. Plausibly, nitration of tyrosine should play a critical role in either conformational or functional changes. If proven in ulterior in vivo studies, this factor would provide another mechanism by which nitrosative stress participates in diabetic complications. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Medical equipment & techniques nationallicence Medical diagnosis nationallicence Diseases & disorders nationallicence Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/8(2003-08-07), 1064-1068 1434-6621 41:8<1064 2003 41 cclm https://doi.org/10.1515/CCLM.2003.164 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/CCLM.2003.164 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Gugliucci Alejandro NATIONALLICENCE 773 0- Clinical Chemistry and Laboratory Medicine Walter de Gruyter 41/8(2003-08-07), 1064-1068 1434-6621 41:8<1064 2003 41 cclm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter