AJP - Heart Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 280: H1821-H1829, 2001;
0363-6135/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (31)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, Y.
Right arrow Articles by Schmaier, A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Y.
Right arrow Articles by Schmaier, A. H.
Vol. 280, Issue 4, H1821-H1829, April 2001

Assembly and activation of HK-PK complex on endothelial cells results in bradykinin liberation and NO formation

Yongqiang Zhao1,*, Qianyao Qiu1,*, Fakhri Mahdi1,*, Zia Shariat-Madar1, Rasmus Røjkjær1, and Alvin H. Schmaier1,2

1 Division of Hematology and Oncology, Department of Internal Medicine and 2 Pathology, University of Michigan, Ann Arbor, Michigan 48109-5669

Prekallikrein (PK) activation on human umbilical endothelial cells (HUVEC) presumably leads to bradykinin liberation. On HUVEC, PK activation requires the presence of cell-bound high-molecular-weight kininogen (HK) and Zn2+. We examined the Zn2+ requirement for HK binding to and the consequences of PK activation on endothelial cells. Optimal HK binding (14 pmol/106 HUVEC) is seen with no added Zn2+ in HEPES-Tyrode buffer containing gelatin versus 16-32 µM added Zn2+ in the same buffer containing bovine serum albumin. The affinity and number of HK binding sites on HUVEC are a dissociation constant of 9.6 ± 1.8 nM and a maximal binding of 1.08 ± 0.26 × 107 sites/cell (means ± SD). PK is activated to kallikrein by an antipain-sensitive mechanism in the presence of HK and Zn2+ on HUVEC, human microvascular endothelial cells, umbilical artery smooth muscle cells, and bovine pulmonary artery endothelial cells. Simultaneous with kallikrein formation, bradykinin (5.0 or 10.3 pmol/106 HUVEC in the absence or presence of lisinopril, respectively) is liberated from cell-bound HK. Liberated bradykinin stimulates the endothelial cell bradykinin B2 receptor to form nitric oxide. Assembly and activation of PK on endothelial cells modulates their physiological activities.

kininogen; prekallikrein; kallikrein; nitric oxide; zinc

* Y. Zhao, Q. Qiu, and F.Mahdi contributed equally to this work.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Wu, V. Rizzo, Y. Liu, I. M. Sainz, N. G. Schmuckler, and R. W. Colman
Kininostatin Associates With Membrane Rafts and Inhibits {alpha}v{beta}3 Integrin Activation in Human Umbilical Vein Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1968 - 1975.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z. Shariat-Madar, F. Mahdi, M. Warnock, J. W. Homeister, S. Srikanth, Y. Krijanovski, L. J. Murphey, A. A. Jaffa, and A. H. Schmaier
Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin
Blood, July 1, 2006; 108(1): 192 - 199.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Shariat-Madar, E. Rahimy, F. Mahdi, and A. H. Schmaier
Overexpression of prolylcarboxypeptidase enhances plasma prekallikrein activation on Chinese hamster ovary cells
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2697 - H2703.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. N. Fernando, L. P. Fernando, Y. Fukuda, and A. P. Kaplan
Assembly, activation, and signaling by kinin-forming proteins on human vascular smooth muscle cells
Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H251 - H257.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z. Shariat-Madar, F. Mahdi, and A. H. Schmaier
Recombinant prolylcarboxypeptidase activates plasma prekallikrein
Blood, June 15, 2004; 103(12): 4554 - 4561.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y. Krijanovski, V. Proulle, F. Mahdi, M. Dreyfus, W. Muller-Esterl, and A. H. Schmaier
Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expression
Blood, June 1, 2003; 101(11): 4430 - 4436.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. R. Baird and P. N. Walsh
Factor XI, but Not Prekallikrein, Blocks High Molecular Weight Kininogen Binding to Human Umbilical Vein Endothelial Cells
J. Biol. Chem., May 30, 2003; 278(23): 20618 - 20623.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
F. Mahdi, Z. S. Madar, C. D. Figueroa, and A. H. Schmaier
Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes
Blood, May 15, 2002; 99(10): 3585 - 3596.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online