AJP - Lung AJP citation statistics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 275: L379-L388, 1998;
1040-0605/98 $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 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 Google Scholar
Google Scholar
Right arrow Articles by Rounds, S.
Right arrow Articles by Cutaia, M. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rounds, S.
Right arrow Articles by Cutaia, M. V.
Vol. 275, Issue 2, L379-L388, August 1998

Mechanism of extracellular ATP- and adenosine-induced apoptosis of cultured pulmonary artery endothelial cells

Sharon Rounds1, Winnie Lin Yee2, Doloretta D. Dawicki1, Elizabeth Harrington1, Nancy Parks1, and Michael V. Cutaia1

1 Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908; and 2 Department of Chemistry, University of Connecticut, West Hartford, Connecticut 06117

Apoptosis may be important in the exacerbation of endothelial cell injury or limitation of endothelial cell proliferation. We have found that extracellular ATP (exATP) and adenosine cause endothelial apoptosis and that the development of apoptosis is linked to intracellular metabolism of adenosine [Dawicki, D. D., D. Chatterjee, J. Wyche, and S. Rounds. Am. J. Physiol. 273 (Lung Cell Mol. Physiol. 17): L485-L494, 1997]. In the present study, we investigated the mechanism of this effect. We found that exATP, adenosine, and the S-adenosyl-L-homocysteine (SAH) hydrolase inhibitor MDL-28842 caused apoptosis and decreased the ratio of S-adenosyl-L-methionine to SAH compared with untreated control cells. Using release of soluble [3H]thymidine as a measure of DNA fragmentation, we found that the effect of adenosine on soluble DNA release was potentiated by coincubation with homocysteine. These results suggest that the mechanism of exATP- and adenosine-induced endothelial cell apoptosis involves inhibition of SAH hydrolase. exATP-induced apoptosis was enhanced by an inhibitor of adenosine deaminase, whereas exogenous adenosine-induced apoptosis was partially inhibited by an adenosine deaminase inhibitor. These results suggest that adenosine deaminase may also be involved in the mechanism of adenosine-induced endothelial cell apoptosis. Adenosine and MDL-28842 caused intracellular acidosis as assessed with the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The cell-permeant base chloroquine prevented adenosine-induced acidosis but not apoptosis. Thus, although intracellular acidosis is associated with adenosine-induced apoptosis, it is not necessary for this effect. We speculate that exATP- and adenosine-induced endothelial cell apoptosis may be due to an inhibition of methyltransferase(s) activity. Purine-induced endothelial cell apoptosis may be important in limiting endothelial cell proliferation after vascular injury.

adenosine 5'-triphosphate; S-adenosyl-L-homocysteine; S-adenosyl-L-methionine; S-adenosyl-L-homocysteine hydrolase; methyltransferase; adenosine kinase; adenosine deaminase; acidosis; sodium/hydrogen antiport; nitric oxide


This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
H. T. Hassoun, M. L. Lie, D. N. Grigoryev, M. Liu, R. M. Tuder, and H. Rabb
Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis
Am J Physiol Renal Physiol, July 1, 2009; 297(1): F125 - F137.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. K. Bradley and M. E. Bradley
Purine Nucleoside-Dependent Inhibition of Cellular Proliferation in 1321N1 Human Astrocytoma Cells
J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 748 - 752.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. IDELL, A. P. MAZAR, P. BITTERMAN, S. MOHLA, and A. L. HARABIN
Fibrin Turnover in Lung Inflammation and Neoplasia
Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 578 - 584.
[Full Text]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. O. Harrington, A. Smeglin, J. Newton, G. Ballard, and S. Rounds
Protein tyrosine phosphatase-dependent proteolysis of focal adhesion complexes in endothelial cell apoptosis
Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L342 - L353.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. O. Harrington, A. Smeglin, N. Parks, J. Newton, and S. Rounds
Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha
Am J Physiol Lung Cell Mol Physiol, October 1, 2000; 279(4): L733 - L742.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Wang, L. Verna, S. Hardy, Y. Zhu, K.-S. Ma, M. J. Birrer, and M. B. Stemerman
c-Jun Triggers Apoptosis in Human Vascular Endothelial Cells
Circ. Res., September 3, 1999; 85(5): 387 - 393.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. E. Bellas, E. O. Harrington, K. L. Sheahan, J. Newton, C. Marcus, and S. Rounds
FAK blunts adenosine-homocysteine-induced endothelial cell apoptosis: requirement for PI 3-kinase
Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L1135 - L1142.
[Abstract] [Full Text] [PDF]


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