Human Nitric Oxide Synthase—Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases

Abstract

In various diseases, there is an increased production of the free radicals needed to carry out certain physiological processes but their excessive amounts can cause oxidative stress and cell damage. Enzymes play a major role in the transformations associated with free radicals. One of them is nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO). This enzyme exists in three forms (NOS1, NOS2, NOS3), each encoded by a different gene. The following work presents the most important information on the NOS isoforms and their role in the human body, including NO synthesis in various tissues and cells, intercellular signaling and activities supporting the immune system and regulating blood vessel functions. The role of NOS in pathological conditions such as obesity, diabetes and heart disease is considered. Attention is also paid to the influence of the polymorphisms of these genes, encoding particular isoforms, on the development of these pathologies and the role of NOS inhibitors in the treatment of patients.

ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

“…Numerous pathological conditions characterized by protracted mitochondrial dysfunction are accompanied by increased production of reactive oxygen (ROS) and reactive nitrogen species (RNS) triggering the insurgence of oxidative/nitrosative stress [ 46 , 47 , 48 , 49 ]. If for ROS overproduction mitochondrial malfunctioning is certainly imputed as the main cause [ 50 ], in the case of excessive RNS formation the main origin is linked to overexpression of inducible nitric oxide synthase (iNOS) with a consequent high rate of nitric oxide generation [ 51 ], often mediated by (neuro)inflammatory processes [ 52 , 53 ]. In preclinical and clinical studies of ALS, clear evidence of ROS and RNS-mediated damages have previously been shown [ 54 , 55 , 56 , 57 ] accompanied by a decrease in brain and muscle concentrations of reduced glutathione [ 58 , 59 ], i.e., one of the most important intracellular water-soluble antioxidant and scavenger of excessive formation of nitric oxide and RNS [ 60 ].…”

Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy

“…We found that 66 genes were upregulated in VKH patients but downregulated after GC therapy (Figure 9F), and 40 genes were downregulated in VKH patients but upregulated after GC therapy (Figure 9G). Among these 106 genes, a key gene NOS3 (Nitric oxide synthase), which plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion and platelet aggregation through production of NO in the vascular endothelium (40), was elevated in VKH patients and can be reduced after GC therapy (Figure 9H), suggesting the dysregulated inflammatory response in VKH patients, and the antiinflammatory effect of GC treatment in VKH. effort has been made in elucidating the pathogenesis of VKH (3), the role of different leukocytes in this disease remains incompletely understood.…”

“…NOS3 is one of the several forms of nitric oxide synthase, which catalyzes the formation of nitric oxide (NO). It has been already known that NO is synthesized by many cell types that are involved in immune responses and inflammatory reactions (40), but the role of NO in immune diseases and inflammation is still unclear. It has been reported that the increased serum nitrite (NO surrogate) in patients suffering from active RA is associated with disease activity, inflammatory cytokines, and endothelial function (65).…”

Nitric oxide is induced and required for efficient Kaposi's sarcoma‐associated herpesvirus lytic replication

“…14,21 In addition to iNOS, there are two other isoforms including neuronal NOS (nNOS or NOS1) and endothelial NOS (eNOS or NOS2) in mammalian cells. 16 Both, iNOS and eNOS can be induced by a variety of inflammatory cytokines and can produce micromolar or nanomolar levels of NO. 14,21 The roles of NO in mammals include various physiological responses such as vasodilatation, neurotransmission, and apoptosis.…”

“…NO is a gaseous molecule, which is synthesized by NO synthase (NOS) from arginine 14,21 . In addition to iNOS, there are two other isoforms including neuronal NOS (nNOS or NOS1) and endothelial NOS (eNOS or NOS2) in mammalian cells 16 . Both, iNOS and eNOS can be induced by a variety of inflammatory cytokines and can produce micromolar or nanomolar levels of NO 14,21 .…”