Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil gelatinase associated lipocalin belongs to a family of small proteins, lipocalins, engaged in the transmembrane transportation of lipophylic substances. Originally isolated from specific granules of neutrophils, it was later located in bone marrow cells as well as lung, bronchial and colon epithelial cells. The expression of neutrophil lipocalin in epithelial cells and in body fluids considerably augments during the occurrence of inflammations and some cancers. A modulation of immunity response was thus suggested to be the main function of neutrophil lipocalin as well as the bacteriostatic effect originating from competition between neutrophil lipocalin and bacteria for siderophoric iron. Forming protective complexes with gelatinase B, the neutrophil lipocalin is implicated in regulatory processes of physiological and pathological rebuilding of tissues, mainly in the angiogenesis. The determination of neutrophil lipocalin levels in body fluids able to discriminate between bacterial and viral infections provides a powerful diagnostic tool. The examination of neutrophil lipocalin in the sera and urine of patients at risk of renal failure offers a very early marker of this acute state. Neutrophil lipocalin represents a sensitive non-invasive marker of renal ischemia and in patients with cystic fibrosis the marker of acute pulmonary exacerbation. Discussions have been conducted regarding the role of neutrophil lipocalin as an early marker of pancreatic cancer or of neutrophilic activation in severe cases of bowel diseases.
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PMID:[NGAL--neutrophil gelatinase associated lipocalin in biochemistry, physiology and clinical praxis]. 1675 74

Imaging of enzyme activity is a central goal of molecular imaging. With the introduction of fluorescent smart probes, optical imaging has become the modality of choice for experimental in vivo detection of enzyme activity. Here, we present a novel high-relaxivity nanosensor that is suitable for in vivo imaging of protease activity by magnetic resonance imaging. Upon specific protease cleavage, the nanoparticles rapidly switch from a stable low-relaxivity stealth state to become adhesive, aggregating high-relaxivity particles. To demonstrate the principle, we chose a cleavage motif of matrix metalloproteinase 9 (MMP-9), an enzyme important in inflammation, atherosclerosis, tumor progression, and many other diseases with alterations of the extracellular matrix. On the basis of clinically tested very small iron oxide particles (VSOP), the MMP-9-activatable protease-specific iron oxide particles (PSOP) have a hydrodynamic diameter of only 25 nm. PSOP are rapidly activated, resulting in aggregation and increased T2*-relaxivity.
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PMID:Protease-specific nanosensors for magnetic resonance imaging. 1900 61

Deferoxamine (DFX), a potent iron-chelating agent, reduces brain edema and neuronal cell injury that develop due to the hemolysis cascade. Statins have neuroprotective effects via anti-inflammatory action and increment of cerebral blood flow after intracerebral hemorrhage (ICH). The purpose of this study was to identify the effects of combined DFX and statins treatment in an experimental ICH rat model. The treatments were: intraperitoneal (i.p.) injection of DFX (group I), combined treatment of i.p. DFX and oral statins (group II), statins only (group III) and treatment with vehicle (group IV). Induction of ICH was performed with injection of bacterial collagenase type IV into the left striatum. After removal of the brain, hematoma volume, water content and brain atrophy were measured. Immunohistochemistry in the perihematomal region was performed for identification of microglial infiltration, astrocyte expression and apoptotic cell presence. Statistical analysis was performed using the non-parametric Kruskal-Wallis test and significance was evaluated when the p value was less than 0.05. According to behavioral tests, significant differences among treatment groups were noted 4 weeks after ICH induction (p < 0.05). However, there were no significant differences among treatment groups in hematoma volume, brain water content or brain atrophy. In the perihematomal area, the activated microglial cells were reduced in the combined treatment group. Among the four groups, a significant difference in immunohistochemical staining was identified (p < 0.05). These results suggest that combined treatment with DFX and statins improves neurologic outcomes after ICH through reduction of microglial infiltration, apoptosis, inflammation and brain edema.
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PMID:Effects of statin and deferoxamine administration on neurological outcomes in a rat model of intracerebral hemorrhage. 2186 69

Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is a 178-amino acid protein which exists in three molecular forms, including a 25-kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of the kidney are the most representative cellular sources. As such, NGAL is now considered the biochemical gold standard for early diagnosis of acute kidney injury. Recent evidence suggests, however, that ectopic or enhanced expression of NGAL may occur in many other pathologic conditions including cancer. Several epidemiologic studies, as reviewed in this chapter, showed that a variety of malignant tumors consistently overexpressed NGAL with increased concentration in blood, urine, and other biologic fluids. In addition, NGAL was frequently associated with tumor size, stage, and invasiveness. These features thus make it a potential biomarker for malignancy. A number of experimental studies also demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells along with the effect on subcellular localization of transmembrane proteins such as cadherins and catenins, confers this protein the potential to enhance can cer aggressiveness and makes it an appealing target of future anticancer research.
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PMID:Neutrophil gelatinase-associated lipocalin in cancer. 2493 19

Traumatic brain injury (TBI), which leads to disability, dysfunction, and even death, is a prominent health problem worldwide with no effective treatment. A brain-permeable flavonoid named (-)-epicatechin (EC) modulates redox/oxidative stress and has been shown to be beneficial for vascular and cognitive function in humans and for ischemic and hemorrhagic stroke in rodents. Here we examined whether EC is able to protect the brain against TBI-induced brain injury in mice and if so, whether it exerts neuroprotection by modulating the NF-E2-related factor (Nrf2) pathway. We used the controlled cortical impact model to mimic TBI. EC was administered orally at 3h after TBI and then every 24h for either 3 or 7 days. We evaluated lesion volume, brain edema, white matter injury, neurologic deficits, cognitive performance and emotion-like behaviors, neutrophil infiltration, reactive oxygen species (ROS), and a variety of injury-related protein markers. Nrf2 knockout mice were used to determine the role of the Nrf2 signaling pathway after EC treatment. In wild-type mice, EC significantly reduced lesion volume, edema, and cell death and improved neurologic function on days 3 and 28; cognitive performance and depression-like behaviors were also improved with EC administration. In addition, EC reduced white matter injury, heme oxygenase-1 expression, and ferric iron deposition after TBI. These changes were accompanied by attenuation of neutrophil infiltration and oxidative insults, reduced activity of matrix metalloproteinase 9, decreased Keap 1 expression, increased Nrf2 nuclear accumulation, and increased expression of superoxide dismutase 1 and quinone 1. However, EC did not significantly reduce lesion volume or improve neurologic deficits in Nrf2 knockout mice after TBI. Our results show that EC protects the TBI brain by activating the Nrf2 pathway, inhibiting heme oxygenase-1 protein expression, and reducing iron deposition. The latter two effects could represent an Nrf2-independent mechanism in this model of TBI.
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PMID:Cerebroprotection of flavanol (-)-epicatechin after traumatic brain injury via Nrf2-dependent and -independent pathways. 2672 90

Neutrophil gelatinase associated lipocalin (NGAL), was originally identified in neutrophil granules as a heterodimer complex with gelatinase B (matrix metalloproteinase 9, MMP9), but more recently has been found to be secreted by damaged epithelial cells. Ngal is a member of the lipocalin family and subsequently named as lipocalin 2 on the basis of structural similarity with other members of the lipocalin family and its potential association with hydrophobic retinol and cholesterol oleate more strongly than their hydrophilic counterparts. In 2002, a landmark paper suggested that Ngal is a bacteriostatic agent which blocks iron acquisition by interacting with a number of bacterial siderophores, especially enterobactin. Since then, more siderophore-carrying functions have been reported than the possibility of hydrophobic ligand transport. In this setting, Ngal was renamed Siderocalin. Functions of siderocalin include not only bacteriostatic activity but potentially as a mediator of cell growth and differentiation; some of these functions appear to be referable to the holo siderocalin:siderophore:iron complex and recent work suggests that metabolic products may act as mammalian siderophores bound by Ngal. While still speculative, it may be that the mammalian siderophores can establish the missing link between Ngal and a number of its functions in vivo. This review provides an overview of the discoveries of the different ligands of Ngal and consequently related functions. Hydrophobic ligands, bacterial siderophores as well as their modified structures (synthetic siderophores), and mammalian siderophores are summarized.
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PMID:The Ligands of Neutrophil Gelatinase-Associated Lipocalin. 2761 81

Wasting marmoset syndrome (WMS) has high incidence and mortality rates and is one of the most important problems in captive common marmoset (Callithrix jacchus) colonies. Despite several reports on WMS, little information is available regarding its reliable treatment. We previously reported that marmosets with WMS had high serum levels of matrix metalloproteinase 9 (MMP9). MMP9 is thought to be a key enzyme in the pathogenesis of inflammatory bowel disease, the main disease state of WMS, and is activated by plasmin, a fibrinolytic factor. In a previous study, treating mice with an antibody to inhibit plasmin prevented the progression of inflammatory bowel disease. Here we examined the efficacy of tranexamic acid, a commonly used plasmin inhibitor, for the treatment of WMS, with supportive measures including amino acid and iron formulations. Six colony marmosets with WMS received tranexamic acid therapy with supportive measures for 8 wk. The body weight, Hct, and serum albumin levels of these 6 marmosets were increased and serum MMP9 levels decreased after this regimen. Therefore, tranexamic acid therapy may be a new and useful treatment for WMS.
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PMID:Tranexamic Acid and Supportive Measures to Treat Wasting Marmoset Syndrome. 2830 50

Obesity causes brain injuries with inflammatory and structural changes, leading to neurodegeneration. Although increased circulating lipocalin 2 (LCN2) level has been implicated in neurodegenerative diseases, the precise mechanism of neurodegeneration in obesity is not clear. Here, we investigated whether LCN2-mediated signaling promotes neurodegeneration in the hippocampus of leptin-deficient ob/ob mice, which are characterized by obesity, insulin resistance, systemic inflammation, and neuroinflammation. In particular, there was significant upregulation of both LCN2 and matrix metalloproteinase 9 levels from serum and hippocampus in ob/ob mice. Using RNA-seq analysis, we found that neurodegeneration- sortilin-related receptor 1 (Sorl1) and brain-derived neurotrophic factor (Bdnf) genes were significantly reduced in the hippocampus of ob/ob mice. We additionally found that the endosome-related WD repeat and FYVE-domain-containing 1 (Wdfy1) gene were upregulated in ob/ob mice. In particular, iron overload-related mitochondrial ferritin and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) proteins were increased in the hippocampus of ob/ob. Thus, these findings indicate that iron-binding protein LCN2-mediated oxidative stress promotes neurodegeneration in ob/ob mice.
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PMID:Hippocampal Lipocalin 2 Is Associated With Neuroinflammation and Iron-Related Oxidative Stress in ob/ob Mice. 3229 47