S-nitrosothiols inhibit uterine smooth muscle cell proliferation independent of
metabolism to NO and cGMP formation.
Cornwell, Trudy L., Erin K. Ceaser, Jie Li, Kevin L. Marrs, Victor M. Darley-Usmar, and
Rakesh P. Patel.
1Division of Molecular and Cellular Pathology, Department of Pathology and
2Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham,
Alabama 35294
APStracts 10:0069C, 2003.
S-nitrosothiols (RSNOs) are important mediators of nitric oxide (NO) biology. The two
mechanisms that appear to dominate in their biological effects are metabolism leading to
the formation of NO and S-nitrosation of protein thiols. In this study we demonstrate that
RSNOs inhibit uterine smooth muscle cell proliferation independent of NO. The
antiproliferative effects of NO on vascular smooth muscle are well defined, with the
classic NO-dependent production of cGMP being demonstrated as the active pathway.
However, less is known on the role of NO in mediating uterine smooth muscle cell
function, a process that is important during menstruation and pregnancy. The RSNOs S-
nitrosoglutathione and S-nitroso-N-acetyl pencillamine inhibited growth factor-dependent
proliferation of human and rat uterine smooth muscle cells (ELT-3). Interestingly, these
cells reduced RSNOs to generate NO. However, use of NO donors and other activators of
the cGMP pathway failed to inhibit proliferation. These findings demonstrate the tissue-
specific nature of responses to NO and demonstrate the presence of a RSNO-dependent
but NO-independent pathway of inhibiting DNA synthesis in uterine smooth muscle
cells.
Received 10 June 2002; accepted in final form 7 February 2003
APS Manuscript Number C268-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003