| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pediatrics, Northwestern University, Chicago, IL, USA
2 Department of Pediatrics, Northwestern University, Chicago, IL, USA; Department of Molecular Pharmacology, Northwestern University, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: steveblack{at}northwestern.edu.
Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are known to play an important role in the proliferation and viability of vascular smooth muscle cells. In this study we determined the effects of increased superoxide dismutase and catalase activity on fetal pulmonary arterial smooth muscle cell (FPASMC) proliferation and viability using EUK-134, a superoxide dismutase/catalase mimetic. Treatment of FPASMC with EUK-134, or with a combination of superoxide dismutase and catalase enzymes, decreased superoxide and hydrogen peroxide levels as detected by the fluorescent dyes dihydroethidium and dichlorodihydrofluorescein diacetate respectively. 5µM EUK-134 attenuated serum-induced FPASMC proliferation, while 50µM EUK-134 decreased the number of viable cells, suggesting cell death. Conversely, combined superoxide dismutase and catalase enzyme activity equivalent to 50µM EUK-134 prevented proliferation but did not reduce the number of viable FPASMC. The loss of mitochondrial membrane potential after 18 hours, an increase in caspase-9 and caspase-3 activity after 24 hours and the subsequent appearance of TUNEL-positive nuclei were detected in FPASMC after treatment with 50µM EUK-134. This indicates an induction of programmed rather than necrotic cell death, and suggests that prolonged removal of ROS is required to stimulate apoptosis. Compounds such as EUK-134 may therefore prove more effective than enzymic anti-oxidants over longer periods, especially when the aim is to decrease the number of smooth muscle cells in diseases resulting from excessive muscularization.
This article has been cited by other articles:
|
|
 |
|
  D. A. Wiseman, S. M. Wells, M. Hubbard, J. E. Welker, and S. M. Black Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L165 - L177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wedgwood, R. H. Steinhorn, M. Bunderson, J. Wilham, S. Lakshminrusimha, L. A. Brennan, and S. M. Black Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L660 - L666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wedgwood and S. M. Black Endothelin-1 decreases endothelial NOS expression and activity through ETA receptor-mediated generation of hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L480 - L487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Patil, M. Bunderson, J. Wilham, and S. M. Black Important role for Rac1 in regulating reactive oxygen species generation and pulmonary arterial smooth muscle cell growth Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1314 - L1322. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
