Abstract
Background: Nitric oxide (NO), a highly versatile signaling molecule, exerts a broad range of regulatory influences in the cardiovascular system that extends from vasodilation to myocardial contractility, angiogenesis, inflammation, and energy metabolism. Considerable attention has been paid to deciphering the mechanisms for such diversity in signaling. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its actions. An emerging concept of NO pathophysiology is that the interplay between NO and reactive oxygen species (ROS), the nitroso/redox balance, is an important regulator of cardiovascular homeostasis. Scope of review: ROS react with NO, limit its bioavailability, and compete with NO for binding to the same thiol in effector molecules. The interplay between NO and ROS appears to be tightly regulated and spatially confined based on the co-localization of specific NO synthase (NOS) isoforms and oxidative enzymes in unique subcellular compartments. NOS isoforms are also in close contact with denitrosylases, leading to crucial regulation of S-nitrosylation. Major conclusions: Nitroso/redox balance is an emerging regulatory pathway for multiple cells and tissues, including the cardiovascular system. Studies using relevant knockout models, isoform specific NOS inhibitors, and both in vitro and in vivo methods have provided novel insights into NO- and ROS-based signaling interactions responsible for numerous cardiovascular disorders. General significance: An integrated view of the role of nitroso/redox balance in cardiovascular pathophysiology has significant therapeutic implications. This is highlighted by human studies where pharmacologic manipulation of oxidative and nitrosative pathways exerted salutary effects in patients with advanced heart failure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.
| Original language | English |
|---|---|
| Pages (from-to) | 752-762 |
| Number of pages | 11 |
| Journal | Biochimica et Biophysica Acta - General Subjects |
| Volume | 1820 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2012 |
Fingerprint
Keywords
- Adrenergic contractility
- Angiogenesis
- Excitation-contraction coupling
- Inflammation
- Nitric oxide
- Nitrosative and oxidative stress
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Regulation of cardiovascular cellular processes by S-nitrosylation. / Schulman, Ivonne H; Hare, Joshua.
In: Biochimica et Biophysica Acta - General Subjects, Vol. 1820, No. 6, 01.06.2012, p. 752-762.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of cardiovascular cellular processes by S-nitrosylation
AU - Schulman, Ivonne H
AU - Hare, Joshua
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Background: Nitric oxide (NO), a highly versatile signaling molecule, exerts a broad range of regulatory influences in the cardiovascular system that extends from vasodilation to myocardial contractility, angiogenesis, inflammation, and energy metabolism. Considerable attention has been paid to deciphering the mechanisms for such diversity in signaling. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its actions. An emerging concept of NO pathophysiology is that the interplay between NO and reactive oxygen species (ROS), the nitroso/redox balance, is an important regulator of cardiovascular homeostasis. Scope of review: ROS react with NO, limit its bioavailability, and compete with NO for binding to the same thiol in effector molecules. The interplay between NO and ROS appears to be tightly regulated and spatially confined based on the co-localization of specific NO synthase (NOS) isoforms and oxidative enzymes in unique subcellular compartments. NOS isoforms are also in close contact with denitrosylases, leading to crucial regulation of S-nitrosylation. Major conclusions: Nitroso/redox balance is an emerging regulatory pathway for multiple cells and tissues, including the cardiovascular system. Studies using relevant knockout models, isoform specific NOS inhibitors, and both in vitro and in vivo methods have provided novel insights into NO- and ROS-based signaling interactions responsible for numerous cardiovascular disorders. General significance: An integrated view of the role of nitroso/redox balance in cardiovascular pathophysiology has significant therapeutic implications. This is highlighted by human studies where pharmacologic manipulation of oxidative and nitrosative pathways exerted salutary effects in patients with advanced heart failure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.
AB - Background: Nitric oxide (NO), a highly versatile signaling molecule, exerts a broad range of regulatory influences in the cardiovascular system that extends from vasodilation to myocardial contractility, angiogenesis, inflammation, and energy metabolism. Considerable attention has been paid to deciphering the mechanisms for such diversity in signaling. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its actions. An emerging concept of NO pathophysiology is that the interplay between NO and reactive oxygen species (ROS), the nitroso/redox balance, is an important regulator of cardiovascular homeostasis. Scope of review: ROS react with NO, limit its bioavailability, and compete with NO for binding to the same thiol in effector molecules. The interplay between NO and ROS appears to be tightly regulated and spatially confined based on the co-localization of specific NO synthase (NOS) isoforms and oxidative enzymes in unique subcellular compartments. NOS isoforms are also in close contact with denitrosylases, leading to crucial regulation of S-nitrosylation. Major conclusions: Nitroso/redox balance is an emerging regulatory pathway for multiple cells and tissues, including the cardiovascular system. Studies using relevant knockout models, isoform specific NOS inhibitors, and both in vitro and in vivo methods have provided novel insights into NO- and ROS-based signaling interactions responsible for numerous cardiovascular disorders. General significance: An integrated view of the role of nitroso/redox balance in cardiovascular pathophysiology has significant therapeutic implications. This is highlighted by human studies where pharmacologic manipulation of oxidative and nitrosative pathways exerted salutary effects in patients with advanced heart failure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.
KW - Adrenergic contractility
KW - Angiogenesis
KW - Excitation-contraction coupling
KW - Inflammation
KW - Nitric oxide
KW - Nitrosative and oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84860447270&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860447270&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2011.04.002
DO - 10.1016/j.bbagen.2011.04.002
M3 - Article
C2 - 21536106
AN - SCOPUS:84860447270
VL - 1820
SP - 752
EP - 762
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
SN - 0304-4165
IS - 6
ER -