Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Abstract

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental.

Meconium-induced inflammation and surfactant inactivation: specifics of molecular mechanisms

“…For example, increase of free radicals activates NF-κB in several cell types (63) resulting in cytokine formation and NOS expression (64,65). Polymorphonuclear NADPH oxidasederived reactive oxygen species (ROS) appear to regulate TLR4 gene expression in EnC which in turn leads to EnC NADPH oxidase (NADPHox) activation (38).…”

Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities

“…Nitric oxide (NO) is synthesized by nitric oxide synthase (NOS) (EC: 1.14.13.39) through oxidation of L-arginine to L-citrulline [1][2][3][4][5]. NO is a biologically significant molecule for many species from bacteria to mammals.…”

“…Neuronal NOS (nNOS, NOS1) is a Ca +2 -dependent, ~160 kDa enzyme that is found in the central and peripheral nervous system cells and striated muscle [4,8]. Inducible NOS (iNOS, NOS2) is a calcium-insensitive, ~130 kDa enzyme that was first isolated from activated macrophages and that can be activated by some cytokines (IL-1, TNF, IF-γ) or bacterial endotoxins [4,9,10].…”

“…Endothelial NOS (eNOS, NOS3) is a Ca +2 /calmodulin-dependent, ~135 kDa enzyme that is localized in vascular endothelial cells, hippocampal neural cells, pulmonary and renal epithelial cells, and cardiac myocytes [4,9,11].…”

“…Three different types of NOS isoforms have been isolated from different tissues, such as vascular endothelium, brain, macrophage, and urinary system, of mammals, including (a) neuronal NOS (nNOS), (b) inducible NOS (iNOS), and (c) endothelial NOS (eNOS) [5,7]. Neuronal NOS (nNOS, NOS1) is a Ca +2 -dependent, ~160 kDa enzyme that is found in the central and peripheral nervous system cells and striated muscle [4,8]. Inducible NOS (iNOS, NOS2) is a calcium-insensitive, ~130 kDa enzyme that was first isolated from activated macrophages and that can be activated by some cytokines (IL-1, TNF, IF-γ) or bacterial endotoxins [4,9,10].…”