Zinc delays clot lysis by attenuating plasminogen activation and plasmin-mediated fibrin degradation

Thrombosis and Haemostasis
Sara J HendersonJ I Weitz

Abstract

Zinc circulates free in plasma at a concentration of 0.1-2 µM, but its levels increase locally when it is released from activated platelets. Although zinc influences many processes in haemostasis, its effect on fibrinolysis has not been thoroughly investigated. Using a fluorescent zinc-binding probe, we demonstrated that zinc binds tissue-type plasminogen activator (tPA) and plasmin with high affinity (Kd values of 0.2 µM), and surface plasmon resonance studies revealed that zinc binds fibrin with a Kd of 12.8 µM. Zinc had no effect on the affinity of plasminogen or plasmin for fibrin, but increased the affinity of tPA by two-fold. In the presence of 5 µM zinc, the catalytic efficiency of plasminogen activation by tPA was reduced by approximately two-fold, both in the absence or presence of fibrin. Zinc attenuated plasmin-mediated degradation of the fibrinogen alpha-chain by 43 %, but had no effect on trypsin degradation. tPA-mediated fibrin clot lysis was prolonged 2.5-fold by zinc in a concentration-dependent fashion, and tPA-mediated plasma clot lysis was attenuated by 1.5-fold. Therefore, our data indicate that zinc modulates fibrinolysis by attenuating tPA-mediated plasminogen activation and plasmin-induced fibrin degradat...Continue Reading

References

Mar 1, 1991·The Journal of Clinical Investigation·A P SappinoD Belin
May 1, 1990·Thrombosis Research·P HopmeierG Marx
Oct 1, 1988·Archives of Biochemistry and Biophysics·G Marx
Aug 1, 1986·American Journal of Hematology·G Marx, P Hopmeier
Jun 1, 1985·American Journal of Hematology·G Marx, A Eldor
Sep 1, 1984·Journal of Clinical Pathology·J W Foote, H T Delves
Dec 1, 1984·The Journal of Clinical Investigation·E G LevinL A Harker
Sep 1, 1993·Journal of Cellular Physiology·G MarxR Gorodetsky
Jan 1, 1993·Physiological Reviews·B L Vallee, K H Falchuk
Mar 1, 1993·American Journal of Hematology·R GorodetskyG Marx
Jun 3, 1999·Proceedings of the Association of American Physicians·R Rojkjaer, A H Schmaier
Sep 14, 2000·Proceedings of the National Academy of Sciences of the United States of America·C M LowS F Traynelis
Feb 14, 2004·Molecular and Cellular Neurosciences·Mustafa M Siddiq, Stella E Tsirka
Oct 31, 2007·Biological Trace Element Research·Sławomir TubekIwona Tubek
Nov 22, 2008·Biochemical Society Transactions·Jin LuClaudia A Blindauer
Dec 8, 2010·Cellular and Molecular Life Sciences : CMLS·Johann Schaller, Simon S Gerber
Dec 15, 2010·Inorganic Chemistry·Artur KreżelWojciech Bal
Jul 5, 2011·Nature Neuroscience·Chihiro NozakiBrigitte L Kieffer
Oct 23, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Ryan W Muthard, Scott L Diamond
Jan 12, 2013·Thrombosis and Haemostasis·Trang T VuJeffrey I Weitz
Aug 31, 2013·The Journal of Biological Chemistry·James C FredenburghJeffrey I Weitz

❮ Previous
Next ❯

Citations

Oct 23, 2015·Thrombosis and Haemostasis·S J HendersonJ I Weitz
Aug 23, 2018·Metallomics : Integrated Biometal Science·Amélie I S SobczakAlan J Stewart
Jan 30, 2020·International Journal of Molecular Sciences·Shin Bi OhJoo-Yong Lee
Jun 7, 2019·Scientific Reports·Sanjeev Kiran GotruAttila Braun
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jing XiaDavid A Weitz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.