Am J Physiol Cell Physiol AJP: Lung Cellular and Molecular Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 279: C1168-C1176, 2000;
0363-6143/00 $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 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 Web of Science (23)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buckley, B. J.
Right arrow Articles by Whorton, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buckley, B. J.
Right arrow Articles by Whorton, A. R.
Vol. 279, Issue 4, C1168-C1176, October 2000

Adaptive responses to peroxynitrite: increased glutathione levels and cystine uptake in vascular cells

Barbara J. Buckley and A. Richard Whorton

Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

We and others recently demonstrated increased glutathione levels, stimulated cystine uptake, and induced gamma -glutamylcysteinyl synthase (gamma -GCS) in vascular cells exposed to nitric oxide donors. Here we report the effects of peroxynitrite on glutathione levels and cystine uptake. Treatment of bovine aortic endothelial and smooth muscle cells with 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, resulted in transient depletion of glutathione followed by a prolonged increase beginning at 8-9 h. Concentration-dependent increases in glutathione of up to sixfold occurred 16-18 h after 0.05-2.5 mM SIN-1. Responses to SIN-1 were inhibited by copper-zinc superoxide dismutases and manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride, providing evidence for peroxynitrite involvement. Because glutathione synthesis is regulated by amino acid availability, we also studied cystine uptake. SIN-1 treatment resulted in a prolonged increase in cystine uptake beginning at 6-9 h. Increases in cystine uptake after SIN-1 were blocked by inhibitors of protein and RNA synthesis, by extracellular glutamate but not by extracellular sodium. These studies suggest induction of the xc- pathway of amino acid uptake. A close correlation over time was observed for increases in cystine uptake and glutathione levels. In summary, vascular cells respond to chronic peroxynitrite exposure with adaptive increases in cellular glutathione and cystine transport.

endothelial cells; smooth muscle cells


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
J. Zhu, S. Li, Z. M. Marshall, and A. R. Whorton
A cystine-cysteine shuttle mediated by xCT facilitates cellular responses to S-nitrosoalbumin
Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1012 - C1020.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. E. Mann, D. J. Rowlands, F. Y.L. Li, P. de Winter, and R. C.M. Siow
Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression
Cardiovasc Res, July 15, 2007; 75(2): 261 - 274.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
G. Gras, F. Porcheray, B. Samah, and C. Leone
The glutamate-glutamine cycle as an inducible, protective face of macrophage activation
J. Leukoc. Biol., November 1, 2006; 80(5): 1067 - 1075.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
G. E. Mann, D. L. Yudilevich, and L. Sobrevia
Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells
Physiol Rev, January 1, 2003; 83(1): 183 - 252.
[Abstract] [Full Text] [PDF]


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