Study on NO signaling pathway and NOS synthase
Nitric oxide (NO) is an autocrine and paracrine signaling pathway molecule that can diffuse into biofilms. It acts for a short time (a few seconds), and its main physiological function is to promote blood vessel homeostasis. It can inhibit smooth muscle contraction and growth , Prevent platelet aggregation and prevent leukocyte-endothelial cell adhesion. In addition, it is also involved in immune defense system, nerve transmission, angiogenesis and other processes. Downstream targets of NO include guanylate cyclase and NF-κB, the former can increase cGMP levels The latter is expressed as an important transcription factor in the iNOS gene. Disorders of NO levels and signals in the body often occur in certain disease states. Diabetic patients have lower NO levels than in the world, and atherosclerosis often leads to damage of the NO signaling pathway. Therefore, the study of NO signaling pathway is of great significance.
NO signaling pathway and NOS synthase:
Nitric oxide (NO) is produced by the oxidation of L-arginine by nitric oxide synthase (NOS). Because the half-life of NO is very short (about 5s), most of the research on NO function is based on NOS activity. Regulation is the basis. The development of inhibitors that target NOS not only can clarify the mechanism of the NO signaling pathway, but also an important idea for the development of drugs for the treatment of diseases caused by NO.
Total NOS (Nitric Oxide Synthase) Inhibitor
Table 1 Total NOS (Nitric Oxide Synthase) Inhibitors
There are currently three types of NOS involved in the normal physiological or pathological processes of NO: nNOS (neuronal / Type I / NOS-1 / bNOS), eNOS (endothelial / Type III / NOS-3) and iNOS (inducible / Type II / NOS-2).
nNOS (neural nitric oxide synthase) inhibitor
nNOS, together with iNOS and eNOS, catalyzes the production of NO and L-citrulline by L-arginine and molecular oxygen. The calcium ion concentration in the body exceeds 100 nm to activate enzyme activity, and the catalytic reaction of the enzyme requires the cofactor tetrahydrobiopterin H4B), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and NADPH.
nNOS's transcriptional regulation mechanism is very complicated.The nNOS gene generates multiple mRNA transcripts through variable promoters, selective splicing, cassette insertion / deletion, 3-UTR cleavage site changes, and polyadenylation. Changes in the amino acid sequence, which translates into nNOS subtypes with different structural and functional characteristics.
nNOS is involved in a series of physiological and pathological processes, including neurotransmission, neurotoxicity, skeletal muscle contraction, sexual function, homeostasis of body fluid and atherosclerosis. nNOS is widely expressed in various tissues, and the human gene encoding nNOS Chromosome 12q14 ..
Table 2 nNOS (neural nitric oxide synthase) inhibitors
In vivo experiment: √
In vivo experiment: √
In vivo experiment: √
eNOS (Endothelial Nitric Oxide Synthase) Inhibitor
eNOS, together with iNOS and nNOS, catalyzes the production of NO and L-citrulline by L-arginine and molecular oxygen. The calcium ion concentration in the body exceeds 100 nm to activate enzyme activity, and the catalytic reaction of the enzyme requires the cofactor tetrahydrobiopterin ( H4B), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and NADPH.
The regulation of eNOS expression is closely related to co-translational / post-translational liposome modification, phosphorylation of Akt / PKB, PKA, AMPK proteins and protein-protein interaction. Hsp90 and Cav-1 in Golgi, regulation of NOSIP and NOSTRIN on the plasma membrane Negative protein-protein interactions, while dynamin, perforin and soluble guanylate cyclase positively regulate eNOS activity.
eNOS is an extremely important regulator of cardiovascular homeostasis, which can regulate the diameter of blood vessels and maintain the anti-proliferation and anti-apoptotic environment of the vasculature. The human gene encoding eNOS is located on chromosome 7q36.
Table 3 eNOS (Endothelial Nitric Oxide Synthase) Inhibitors
iNOS (Inducible Nitric Oxide Synthase) Inhibitor
iNOS, together with nNOS and eNOS, catalyzes the production of NO and L-citrulline by L-arginine and molecular oxygen. High affinity binds Ca2 + / calmodulin for continuous activation. The catalytic reaction of the enzyme requires the cofactor tetrahydrobiological The participation of pterin (H4B), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and NADPH.
iNOS gene expression is regulated by various signaling pathways, including NF-κB, IFN-γ (signaling through JAK-STAT cascade system) and HIF-1, which induce gene expression. There are also TGF-β, IL-4, IL -10 and IL-13, inhibit gene expression. NAP110 (NOS binding protein) prevents iNOS from homodimerization for post-translational regulation.
iNOS plays an important role in the innate immune system, with antibacterial, antifungal and antiviral activities. The human gene encoding iNOS is located on the chromosome
Toilet Paper,Jumbo Toilet Rolls Wholesale,Four Ply Toilet Paper,Compact Toilet Paper
DONGGUAN YEE HUP TRADING CO,.LTD , https://www.yeehupack.com