Abstract |
Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro- L-arginine methyl ester ( L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection.
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Authors | Junhui Sun, Angel M Aponte, Mark J Kohr, Guang Tong, Charles Steenbergen, Elizabeth Murphy |
Journal | Free radical biology & medicine
(Free Radic Biol Med)
Vol. 54
Pg. 105-12
(Jan 2013)
ISSN: 1873-4596 [Electronic] United States |
PMID | 22989471
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Copyright | Published by Elsevier Inc. |
Chemical References |
- 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
- Carbazoles
- Oxadiazoles
- Quinoxalines
- KT 5823
- Nitric Oxide
- Cyclic GMP-Dependent Protein Kinases
- Guanylate Cyclase
- Ascorbic Acid
- NG-Nitroarginine Methyl Ester
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Topics |
- Animals
- Ascorbic Acid
(administration & dosage)
- Carbazoles
(administration & dosage)
- Cells, Cultured
- Cyclic GMP-Dependent Protein Kinases
(antagonists & inhibitors, metabolism)
- Guanylate Cyclase
(antagonists & inhibitors, metabolism)
- Ischemic Preconditioning, Myocardial
- Male
- Mice
- Mice, Inbred C57BL
- Myocardium
(metabolism, pathology)
- NG-Nitroarginine Methyl Ester
(administration & dosage)
- Nitric Oxide
(metabolism)
- Nitrosation
- Organ Culture Techniques
- Oxadiazoles
(administration & dosage)
- Quinoxalines
(administration & dosage)
- Reperfusion Injury
(prevention & control)
- Signal Transduction
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