Nitric oxide synthases, S-nitrosylation and cardiovascular health: From molecular mechanisms to therapeutic opportunities (Review)

Abstract

The understanding of nitric oxide (NO) signaling has grown substantially since the identification of endothelial derived relaxing factor (EDRF). NO has emerged as a ubiquitous signaling molecule involved in diverse physiological and pathological processes. Perhaps the most significant function, independent of EDRF, is that of NO signaling mediated locally in signaling modules rather than relying upon diffusion. In this context, NO modulates protein function via direct post-translational modification of cysteine residues. This review explores NO signaling and related reactive nitrogen species involved in the regulation of the cardiovascular system. A critical concept in the understanding of NO signaling is that of the nitroso-redox balance. Reactive nitrogen species bioactivity is fundamentally linked to the production of reactive oxygen species. This interaction occurs at the chemical, enzymatic and signaling effector levels. Furthermore, the nitroso-redox equilibrium is in a delicate balance, involving the cross-talk between NO and oxygen-derived species signaling systems, including NADPH oxidases and xanthine oxidase.

Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine-Specific Phosphonate Adaptable Tag in Combination with TiO2 Chromatography

“…S-nitrosylation is emerging as a key post-translational protein modification involved in regulation of physiological and pathological cell functions, from neurological and cardiovascular disorders to oncogenesis and tumor progression (8,9,(11)(12)(13)(14)(36)(37)(38).…”

“…S-nitrosylation influences protein stability, conformational changes and activity (3)(4)(5)(6)(7). In physiological conditions, NO acts as a signaling molecule in the cardiovascular, nervous and immune systems (8)(9)(10). However, the excessive production of NO associated to nitrosative/nitrative stress has been linked to cardiovascular and neurodegenerative diseases, as well as inflammatory processes with detrimental outcomes in cancer and other disorders (11)(12)(13).…”

A radical form of nitric oxide inhibits porcine circovirus type 2 replication in vitro

“…NO is a short-lived and reactive free radical that is chemically able to diffuse within biological systems. In mammalian cells, the production of NO is catalyzed by a family of NO synthases (NOSs), which facilitate the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reaction of L-arginine with O 2 , to yield NO and L-citrulline [8]. Besides, NO-generating compounds, such as sodium nitroprusside (SNP), S-nitroso-acetylpenicillamine (SNAP), S-nitrosoglutathion (GNSO) and so on, can also release NO.…”

Gasotransmitters and Protein Post-Translational Modifications

“…7,8 NO may also regulate cellular functions via the activation of soluble guanylyl cyclase (sGC) leading to the production of cyclic guanosine monophosphate (cGMP). 1,2 Up to now, numerous proteins together with the target cysteine residues have been demonstrated.…”

“…7,8 NO plays a relevant role in regulating many cellular functions and pathophysiological responses, including cell growth and apoptosis, inflammation, vasodilation, ischemic damage, and respiration, etc.…”