| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216
To determine whether homocysteine
(Hcy)-mediated activation of endocardial endothelial (EE) cells is
ameliorated by peroxisome proliferator-activated receptor (PPAR), we
isolated EE cells from mouse endocardium. Matrix metalloproteinase
(MMP) activity and intercellular adhesion molecule (ICAM)-1 in EE cells
were measured in the presence and absence of Hcy, and ciprofibrate (CF;
PPAR-
agonist) or 15-deoxy-
12,14-prostaglandin
J2 (PGJ2; PPAR-
agonist) by zymography and
Western blot analyses, respectively. Results suggest that Hcy-mediated MMP activation and ICAM-1 expression are ameliorated by CF and PGJ2. To test the hypothesis that Hcy competes with other
ligands for binding to PPAR and -, we prepared cardiac nuclear
extracts. Extracts were loaded onto an Hcy-cellulose affinity column.
Bound proteins were eluted with CF and PGJ2. To determine
conformational changes in PPAR upon binding to Hcy, we measured PPAR
fluorescence at 334 nm. Dose-dependent increase in PPAR fluorescence
demonstrated a primary binding affinity of 0.32 ± 0.06 µM. There was
dose-dependent quenching of PPAR fluorescence by
fluorescamine-homocysteine (F-Hcy). PPAR- fluorescence quenching was
abrogated by the addition of CF but not by PGJ2. PPAR-
fluorescence quenching was abrogated by the addition of
PGJ2 but not by CF. These results suggest that Hcy competes
with CF and PGJ2 for binding to PPAR- and -,
respectively, indicating a role of PPAR in amelioration of Hcy-mediated
EE dysfunction.
metalloproteinase; prostaglandin; fibrate; leukotriene; receptor; binding; microvessel; hydroxyeicosatetraeonic acid; epoxyeicosatrienoic acid; fluorescence resonance energy transfer
This article has been cited by other articles:
|
|
 |
|
  K. S. Moshal, M. Singh, U. Sen, D. S. E. Rosenberger, B. Henderson, N. Tyagi, H. Zhang, and S. C. Tyagi Homocysteine-mediated activation and mitochondrial translocation of calpain regulates MMP-9 in MVEC Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2825 - H2835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Rodriguez, N. Tyagi, I. G. Joshua, J. C. Passmore, J. T. Fleming, J. C. Falcone, and S. C. Tyagi Pioglitazone mitigates renal glomerular vascular changes in high-fat, high-calorie-induced type 2 diabetes mellitus Am J Physiol Renal Physiol, September 1, 2006; 291(3): F694 - F701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Moshal, U. Sen, N. Tyagi, B. Henderson, M. Steed, A. V. Ovechkin, and S. C. Tyagi Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway Am J Physiol Cell Physiol, March 1, 2006; 290(3): C883 - C891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]
|
|
|
|
 |
|
 S. C. Tyagi, W. Rodriguez, A. M. Patel, A. M. Roberts, J. C. Falcone, J. C. Passmore, J. T. Fleming, and I. G. Joshua Hyperhomocysteinemic Diabetic Cardiomyopathy: Oxidative Stress, Remodeling, and Endothelial-Myocyte Uncoupling Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2005; 10(1): 1 - 10. [Abstract] [PDF]
|
|
|
|
 |
|
 F. M. Faraci Hyperhomocysteinemia: A Million Ways to Lose Control Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 371 - 373. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
