Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis
Name
Sartoretto-2011-Hydrogen peroxide di.pdf
Size
1.07 MB
Format
Adobe PDF
Checksum (MD5)
e708dfe9833c94a02452776108c3d059
Author(s)
Sartoretto, Juliano
Kalwa, Hermann
Pluth, Michael D.
Lippard, Stephen J.
Date Issued
September 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Sartoretto, J. L. et al. “Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis.” Proceedings of the National Academy of Sciences 108.38 (2011): 15792-15797. ©2011 by the National Academy of Sciences
Version
Final published version
Abstract
Nitric oxide (NO) and hydrogen peroxide (H(subscript 2)O(subscript 2)) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases, but the differential roles of these NOS isoforms and the interplay of reactive oxygen species and reactive nitrogen species in cardiac signaling pathways are poorly understood. Using a recently developed NO chemical sensor [Cu(subscript 2)(FL2E)] to study adult cardiac myocytes from wild-type, eNOSnull, and nNOSnull mice, we discovered that physiological concentrations of H(subscript 2)O(subscript 2) activate eNOS but not nNOS. H(subscript 2)O(subscript 2)-stimulated eNOS activation depends on phosphorylation of both the AMP-activated protein kinase and kinase Akt, and leads to the robust phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with lentivirus expressing the recently developed H(subscript 2)O(subscript 2) biosensor HyPer2 show marked H2O2 synthesis when stimulated by angiotensin II, but not following β-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H2O2, whereas β-adrenergic contractile responses occur independently of H(subscript 2)O(subscript 2) signaling. These studies establish differential roles for H(subscript 2)O(subscript 2) in control of cardiac contractility and receptor-dependent NOS activation in the heart, and they identify new points for modulation of NO signaling responses by oxidant stress.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1111331108
