nitric

Human Dynein Cytoplasmic Light Chain 1 (DYNLL1) has been identified as a protein that interacts with NOS1, leading to NOS1 inhibition. NOS1 dimer is destabilized after binding DYNLL1 a conformation necessary activity, and it regulate numerous biologic processes throughits effects on nitric oxide synthase activity. DYNLL1 is widely expressed, with higher expression in testis and moderate expression in brain.

Arginase-2 (ARG2) is a member of the arginase family. Arginase is a manganese-containing enzyme which catalyzes the hydrolysis of arginine to ornithine and urea. ARG2 is highly expressed in kidney and prostate, not founded in the liver, heart and pancreas. ARG2 has been implicated in the regulation of the arginine ornithine concentrations in the cell. ARG2 may take part in the regulation of extra-urea cycle arginine metabolism and in down-regulation of nitric oxide synthesis. The extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase.

Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level.

Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys.; Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion. In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival. Plays a role in the immune response of alternatively activated or M2 macrophages in processes such as wound healing and tissue regeneration, immune defense against multicellular pathogens and parasites, and immune suppression and allergic inflammation; the regulatory outcome seems to be organ specific. In tumor-infiltrating dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) plays a role in suppression of T cell-mediated antitumor immunity.

The recycling of citrulline by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL) is crucial to maintain arginine availability and nitric oxide (NO) production. Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cancer.

Endothelial Differentiation-Related Factor 1 (EDF1) is a 148 amino acid transcriptional coactivator that contains 1 HTH cro C1-type DNA-binding domain. It has been postulated that the protein functions as a bridging molecule that interconnects regulatory proteins and the basal transcriptional machinery, thereby modulating the transcription of genes involved in endothelial differentiation. When endothelial cells are induced to differentiate in vitro, EDF1 is downregulated, leading to inhibition of cell growth and cell polarization. EDF1 binds calmodulin thorough its IQ domain and regulates nitric oxide synthase activity through calmodulin sequestration in the cytoplasm. Though ubiquitously expressed, EDF1 is most abundant in adult liver, heart, adipose tissues, intestine and pancreas. In fetal tissues, EDF1 is most abundant in kidney. There are two isoforms of EDF1 that are produced as a result of alternative splicing events.

Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2 5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2. Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5.

Pancreatic derived factor, also known as FAM3B, is an islet-specific secreted cytokine specifically expressed at high levels in the islets of Langerhans of the endocrine pancreas. FAM3B protein is present in alpha- and beta- cells of pancreatic islets, insulin-secreting beta-TC3 cells, and glucagon-secreting alpha-TC cells. FAM3B causes apoptosis of beta-cells as assessed by electron microscopy, annexin Ⅴ fluorescent staining, and flow-cytometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. FAM3B activated caspase-3 while not affect cytosolic Ca2+levels or nitric oxide levels. Hense, FAM3B may have a role in the process of pancreatic?-cell apoptosis of primary islet and cell lines. FAM3B secretion is regulated by glucose and other insulin secretagogues. This islet-specific secreted cytokine is secreted from both pancreatic alpha- and beta- cells. Glucose stimulates FAM3B secretion dose dependently in beta- cell lines and primary islets but not in alpha-cells. It is likely cosecreted with insulin via the same regulatory mechanisms and structure and conformation is vital for FAM3B secretion.

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. DDAH2 Protein, Human, Recombinant (GST & His) is expressed in E. coli expression system with N-6xHis-GST tag. The predicted molecular weight is 61.2 kDa and the accession number is O95865.

May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells. May suppress inflammation-related signaling in asthmatic airway epithelium. May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism. May play a role in promoting prenatal immune suppression. Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3 eNOS dysfunction. Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling. Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths due to its often late stage diagnosis, and dermcidin (DCD) may have the potential to be used as a serum biomarker for HCC for more timely diagnoses. Human dermcidin (DCD) is an antimicrobial peptide secreted constitutively by sweat glands. And the role of DCD in ischemic heart disease has drawn increasing attention in particular its relationship with insulin secretion and glycemic control, nitric oxide (NO) synthesis and hypertension, platelet aggregation and acute myocardial infarction (AMI).

Thioredoxin (TXN) is a member of the Thioredoxin family. Thioredoxin exists as a disulfide-linked homodimer and contains one Thioredoxin domain. Thioredoxin is up-regulated by ionizing radiation. Thioredoxin participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Thioredoxin also plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide.

cGMP-Dependent Protein Kinase 1 (PRKG1) belongs to the protein kinase superfamily and AGC Ser Thr protein kinase family. PRKG1 contains one AGC-kinase C-terminal domain, two cyclic nucleotide-binding domains, and one protein kinase domain. PRKG1 is mainly expressed in the lung and placenta. PRKG1 acts as a key mediator of the nitric oxide (NO) cGMP signaling pathway. PRKG1 can phosphorylate many proteins that regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm, and nociception.

Thrombospondin-1 (TSP-1) is a 150-180kDa calcium-sensitive protein that is secreted as a disulfide-linked homotrimer. TSP-1 regulates a wide range of cellular functions including their interactions with other cells and with the extracellular matrix (ECM). TSP-1 contains an N-terminal Laminin G-like globular domain, an extended central region with one vWFC domain, 3 TSP type 1domains, 2 EGF-like domains, and 8 TSP type3 domains, and a globular TSP C-terminal domain. Distinct regions of TSP-1 have been associated with binding to particular ECM or cellular molecules. TSP-1 counteracts the angiogenic, hypotensive, and antithrombotic effects of nitric oxide (NO). It binds and neutralizes VEGF, blocks VEGF R2 signaling on vascular endothelial cells(EC), and destabilizes adhesive contacts between EC. TSP-1 also plays an important role in wound repair and tissue fibrosis by binding latent TGF-beta and inducing release of the active cytokine from the latency associated peptide (LAP).

Cytoglobin is a ubiquitously globin protein that belongs to the globin family. The highest expressed in heart, stomach, bladder and small intestine. CYGB acts a protector under conditions of oxidative stress. CYGB may be involved in intracellular oxygen storage or transfer, modulates oxygen and nitric oxide metabolism or scavenging free radicals within a cell.

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. DDAH1 Protein, Human, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 38.4 kDa and the accession number is O94760.

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Specifically regulates nitric-oxide-generated cGMP. PDE5A Protein, Mouse, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 26.1 kDa and the accession number is Q8CG03.