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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sartoretto, Juliano L. Lippard, Stephen J. Kalwa, Hermann Pluth, Michael D. Michel, Thomas |
| Description | Author Affiliation: Sartoretto JL ( Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.); |
| Abstract | Nitric oxide (NO) and hydrogen peroxide (H(2)O(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(2)(FL2E)] to study adult cardiac myocytes from wild-type, eNOS(null), and nNOS(null) mice, we discovered that physiological concentrations of H(2)O(2) activate eNOS but not nNOS. H(2)O(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(2)O(2) biosensor HyPer2 show marked H(2)O(2) synthesis when stimulated by angiotensin II, but not following ß-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H(2)O(2), whereas ß-adrenergic contractile responses occur independently of H(2)O(2) signaling. These studies establish differential roles for H(2)O(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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 38 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Hydrogen Peroxide Pharmacology Myocytes, Cardiac Drug Effects Nitric Oxide Synthase Type III Metabolism Nitric Oxide Synthase Type I AMP-Activated Protein Kinases Antagonists & Inhibitors Adrenergic Beta-Agonists Angiotensin II Animals Cell Size Cells, Cultured Copper Chemistry Fluorescent Dyes Immunoblotting Isoproterenol Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Myocardial Contraction Cytology Enzymology Nitric Oxide Genetics Proto-Oncogene Proteins C-akt Pyrazoles Pyrimidines Vasoconstrictor Agents Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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