In the combined sample of 2,170 MDD cases and 1,810 controls......
In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis. Haplotype analyses applying 2- and 3-SNPs sliding windows using UNPHASED program showed significant global association between NOS2A rs2297518¨Crs8072199¨Crs2779248 haplotype (P=0.017, FDRp=0.026) and MDD.More...
Positive relationships between NOS2 and other components at different levels (count: 0)
Positive relationship network of NOS2 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
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If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
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Negative relationships between NOS2 and MDD (count: 1)
The results demonstrate that the nNOS variants are found at ......
The results demonstrate that the nNOS variants are found at similar frequencies in MDD patients and healthy control subjects. More...
Negative relationships between NOS2 and other components at different levels (count: 0)
Ca2+ that enters the cell from the outside is a principal so......
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).More...
Leishmania is an intracellular protozoan parasite of macroph......
Leishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and proliferate intracellularly by deactivating the macrophage. Successful infection of Leishmania is achieved by alteration of signaling events in the host cell, leading to enhanced production of the autoinhibitory molecules like TGF-beta and decreased induction of cytokines such as IL12 for protective immunity. Nitric oxide production is also inhibited. In addition, defective expression of major histocompatibility complex (MHC) genes silences subsequent T cell activation mediated by macrophages, resulting in abnormal immune responses.More...
Small cell lung carcinoma (SCLC) is a highly aggressive neop......
Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 20% of all lung cancer cases. Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.More...
Peroxisomes are essential organelles that play a key role in......
Peroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contribute to many crucial metabolic processes such as fatty acid oxidation, biosynthesis of ether lipids and free radical detoxification. The biogenesis of peroxisomes starts with the early peroxins PEX3, PEX16 and PEX19 and proceeds via several steps. The import of membrane proteins into peroxisomes needs PEX19 for recognition, targeting and insertion via docking at PEX3. Matrix proteins in the cytosol are recognized by peroxisomal targeting signals (PTS) and transported to the docking complex at the peroxisomal membrane. Peroxisomes' deficiencies lead to severe and often fatal inherited peroxisomal disorders (PD). PDs are usually classified in two groups. The first group is disorders of peroxisome biogenesis which include Zellweger syndrome, and the second group is single peroxisomal enzyme deficiencies.More...
Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)
The most recognized mechanism by which peroxisome proliferat......
The most recognized mechanism by which peroxisome proliferators regulated gene expresssion is through a PPAR/RXR heterodimeric complex binding to a peroxisome proliferator-response element (PPRE) (classical mechanism). However, there are the possibility of several variations on this theme: 1). The peroxisome proliferator interacts with PPAR that preexists as a DNA complex with associated corepressors proteins. The interaction with ligand causes release of the corepressor and association with a coactivator, resulting in the classical mechanism. 2). The peroxisome proliferator interacts with PPAR as a soluble member of the nucleus. The binding of ligand results in RXR heterodimerization, DNA binding and coactivator recruitment. 3). In this scenario, PPAR exists in the cytosol, perhaps complexed to heat shock protein 90 and/or other chaperones. Binding of peroxisome proliferator causes a conformational change and translocation into the nucleus. Scenarios 4 and 5 require regulation of gene expression via non-classical mechanisms: 4). PPAR is capable of interacting with, and forming DNA binding heterodimers with, several nuclear receptors including the thyroid hormone receptor. The binding site for this non-RXR heterodimer need not be the classic DR-1 motif found in the PPRE. 5). PPAR may participate in the regulation of gene expression witout binding to DNA. By association with transcription factors such as c-jun or p65, PPAR diminishes the ability of AP1 or NFB to bind to their cognate DNA sequences, respectively. Also shown in this scheme are two means to modify the peroxisome proliferator response. Most importantly, growth factor signaling has a pronounced affect on PPAR via post-translational modification. PPAR is a phosphoprotein and its activity is affected by insulin. Several kinase pathways affects PPARa's activity, although the specific kinases and phosphorylation sites have not been conclusively determined.More...
Macrophages and NK cells help provide innate immunity agains......
Macrophages and NK cells help provide innate immunity against infection by intracellular parasites and communicate with each other to regulate this process. When stimulated, macrophages secrete the cytokine IL-12 that is essential for activation of the cytotoxic activity of natural killer (NK) cells. IL-12 stimulates this NK cell response through activation of a JAK/STAT signaling pathway. Binding of IL-12 to its receptor on NK cells causes tyrosine phosphorylation and activation of JAK2 and another JAK kinase, Tyk2. Tyk2 in turn phosphorylates the transcription factor STAT4, which can then translocate to the nucleus to activate genes, including the expression of interferon-gamma. IFN-gamma and IL-12 induce the differentiation of TH1 helper T cells that activate macrophages through interferon-gamma. A key modulator of NK cell activation by IL-12 is nitric oxide, NO, produced from arginine by the inducible nitric oxide synthase NOS2. Inactivation of the NOS2 gene in mice impairs the initial innate response to infection, including the activation of NK cells. This phenotype is similar to that of mice lacking interferon-gamma or IL-12 and a similar effect can be produced by inhibiting NOS2 with L-N6-iminoethyl-lysine (L-NIL) during infection, blocking the activation of NK cells by IL-12. NO production does not affect the activation of JAK2 by IL-12, but is required for Tyk2 activity, the downstream activation of STAT-4 and the production of interferon-gamma by NK cells. The role of NO in Tyk2 activation is not yet known, but does not seem to involve change the phosphorylation status of Tyk2. Curiously, activation of T cells by IL-12 does not appear to involved NO production, indicating a distinct mechanism is involved in NK cells. NO also plays a role as a feedback inhibitor of IL-12 production by macrophages, helping to prevent over-activation of the Th1 cells by IL-12. NO appears to make an important contribution to the early innate response to infections before specific immunity is active.More...
NOS2 related Reactome pathways (count: 0)
NOS2 related interactors from protein-protein interaction data in HPRD (count: 8)
Basic Information
Positive relationships between NOS2 and other components at different levels (count: 0)
