| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, New York Medical College, Valhalla 10595; and 2 Department of Pharmacology, State University of New York, Stony Brook, New York 11794
The accumulated ultrastructural and biochemical evidence is highly suggestive of the existence of mitochondrial nitric oxide (NO) synthase (mtNOS), where local production of NO regulates the electron transport along the respiratory chain. Here, the functional competence of mtNOS in situ in a living cell was examined using an intravital fluorescent NO indicator, 4,5-diaminofluorescein, employing a new procedure for loading it into the mitochondria to demonstrate local NO generation in undisrupted endothelial cells and in isolated mitochondria as well as in human embryonic kidney cells stably expressing endothelial NOS. With the use of this approach, we showed that endothelial cells incubated in the presence of high concentration of D-glucose (but not L-glucose) are characterized by the reduced NO synthetic function of mitochondria despite the unaltered abundance of the enzyme. In parallel, mitochondrial generation of superoxide was augmented in endothelial cells incubated in the presence of a high concentration of D-glucose. Both the NO generation and superoxide production in hyperglycemic environment could be restored to control levels by treating cells with a cell-permeable superoxide dismutase mimetic. In addition, enhanced mitochondrial superoxide production could be suppressed with an inhibitor of NOS in stimulated endothelial cells. In conclusion, the data 1) provide direct evidence of mitochondrial NO production in endothelial cells, 2) demonstrate its suppression and enhanced superoxide generation in hyperglycemic environment, and 3) provide evidence that "uncoupled" mtNOS represents an important source of superoxide anions in endothelial cells incubated in high glucose-containing medium.
mitochondria; nitric oxide synthase; superoxide anions
This article has been cited by other articles:
|
|
 |
|
  E. N. Dedkova and L. A. Blatter Characteristics and function of cardiac mitochondrial nitric oxide synthase J. Physiol., February 15, 2009; 587(4): 851 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chen, S.-J. Lin, F.-Y. Lin, T.-C. Wu, C.-R. Tsao, P.-H. Huang, P.-L. Liu, Y.-L. Chen, and J.-W. Chen High Glucose Impairs Early and Late Endothelial Progenitor Cells by Modifying Nitric Oxide-Related but Not Oxidative Stress-Mediated Mechanisms Diabetes, June 1, 2007; 56(6): 1559 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. X. Zhang and D. D. Gutterman Mitochondrial reactive oxygen species-mediated signaling in endothelial cells Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2023 - H2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakagawa, W. Sato, O. Glushakova, M. Heinig, T. Clarke, M. Campbell-Thompson, Y. Yuzawa, M. A. Atkinson, R. J. Johnson, and B. Croker Diabetic Endothelial Nitric Oxide Synthase Knockout Mice Develop Advanced Diabetic Nephropathy J. Am. Soc. Nephrol., February 1, 2007; 18(2): 539 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Davidson and M. R. Duchen Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance Cardiovasc Res, July 1, 2006; 71(1): 10 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakagawa, W. Sato, Y. Y. Sautin, O. Glushakova, B. Croker, M. A. Atkinson, C. C. Tisher, and R. J. Johnson Uncoupling of Vascular Endothelial Growth Factor with Nitric Oxide as a Mechanism for Diabetic Vasculopathy J. Am. Soc. Nephrol., March 1, 2006; 17(3): 736 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Kevin, E. Novalija, and D. F. Stowe Reactive Oxygen Species as Mediators of Cardiac Injury and Protection: The Relevance to Anesthesia Practice Anesth. Analg., November 1, 2005; 101(5): 1275 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Brodsky, F. Zhang, A. Nasjletti, and M. S. Goligorsky Endothelium-derived microparticles impair endothelial function in vitro Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1910 - H1915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Dedkova, X. Ji, S. L. Lipsius, and L. A. Blatter Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells Am J Physiol Cell Physiol, February 1, 2004; 286(2): C406 - C415. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
