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

Abnormalities in extracellular matrix degradation may play a pathogenetic role in diabetic nephropathy. Cultured renal mesangial cells are known to synthesize increased amounts of matrix proteins when incubated in high glucose media (e.g., 30 mmol/l). However, the effect of glucose loading on degradative enzymes is unknown. Primary cultures of rat mesangial cells were grown until confluent in the presence of fetal calf serum (FCS) and insulin (0.67 U/ml). Cells were then cultured for 7 days in plastic wells in either 10 or 30 mmol/l glucose media containing neither FCS nor insulin. Collagenase activity in media were determined by zymography and quantitative spectrofluorometry. Cathepsin B and D activities in cell extracts were measured by spectrofluorometry (using the fluorescent substrate Z-Arg-Arg-7-amido-4-methylcoumarin) and 125I-labeled hemoglobin digestion, respectively. Gelatin-degrading activity of live mesangial cells was also determined. mRNA levels for collagenase IV, cathepsin B, and cathepsin D were determined by Northern analysis. A major band of collagenase activity with a molecular size of 72 kDa was observed in all mesangial cell media. Exposure of cells to high glucose media resulted in significant reductions in collagenase and cathepsin B activities as well as impairment in gelatin-degrading activity. Collagenase IV and cathepsin B and D mRNA levels were also decreased by glucose loading. To exclude the possibility that glucose loading was injurious to cells, 3H-leucine uptake (as a measure of protein synthesis) and membrane alkaline phosphatase activity (as a biochemical marker of viability) were not affected by the high glucose condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased degradative enzymes in mesangial cells cultured in high glucose media. 762 99

[Poly(ethyleneglycol)]-modified hemoglobin vesicles (PEG-HbV), a type of encapsulated hemoglobin, have been developed as artificial oxygen carriers and it is important to evaluate their blood compatibility. We studied the effects of PEG-HbV on human polymor phonuclear neutrophils (PMNs) in vitro, focusing on the functional responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP) as an agonist. The pretreatment of the PMNs with PEG-HbV up to a concentration of 60 mg/dl Hb did not affect the fMLP-triggered chemotactic activity. In parallel to these results, the fMLP-induced upregulation of CD11b (Mac-1) levels on the PEG-HbV-pretreated PMNs was comparable to that of untreated cells. Furthermore, the pretreatment of the PMNs with the PEG-HbV even at 600 mg/dl Hb did not affect the gelatinase B (Matrix methalloproteinase-9 (MMP-9)) release, suggesting that the fMLP-induced release of secondary and tertiary granules was normal. In addition, the fMLP-triggered superoxide production of the PMNs was unchanged by the pretreatment with the PEG-HbV at 600 mg/dl Hb. Thus, these results suggest that PEG-HbV, at the concentrations studied, have no aberrant effects on the fMLP-triggered functions of human PMNs.
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PMID:Effects of poly(ethyleneglycol)-modified hemoglobin vesicles on N-formyl-methionyl-leucyl-phenylalanine-induced responses of polymorphonuclear neutrophils in vitro. 1179 29

Intratumor (i.t.) injection of 35 mg/kg/day NAMI-A for six consecutive days to CBA mice bearing i.m. implants of MCa mammary carcinoma reduces primary tumor growth and particularly lung metastasis formation, causing 60% of animals to be free of macroscopically detectable metastases. The i.t. treatment allows study of the effects of NAMI-A on in vivo tumor cells exposed to millimolar concentrations for a relatively prolonged time. Under these conditions, NAMI-A reduces the number of CD44+ tumor cells and changes tumor cell phenotype to a lower aggressive behavior, as shown by scanning electron microscopy analysis. On primary tumor site, NAMI-A causes unbalance between 2n and aneuploid cells in favor of lymphocytes. Furthermore, in tumor tissue, nitric oxide production is increased and active matrix metalloproteinase 9 is decreased, and these effects are accompanied by a reduced hemoglobin concentration. These data are in agreement with the reduction of tumor invasion and metastasis and suggest the therapeutic usefulness of NAMI-A in neoadjuvant or tumor reduction treatments for preventing metastasis formation. These data further stress the usefulness of intratumor treatments as experimental preclinical model for studying in vivo the mechanism of tumor cell interactions after prolonged exposure to ruthenium-based compounds to be developed for metastasis inhibition.
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PMID:Intratumoral NAMI-A treatment triggers metastasis reduction, which correlates to CD44 regulation and tumor infiltrating lymphocyte recruitment. 1507 81

Plasmodium protozoa, the source of malarial infections, catabolize large quantities of hemoglobin during an intraerythrocytic phase. During this process, free heme is detoxified through biomineralization into an insoluble heme aggregate, hemozoin (Hz). In its native state, Hz is associated with a variety of lipid peroxidation products including 4-hydroxy-2-nonenal (HNE). In the present study, gene expression profiles were used to compare responses to two of the individual components of Hz in a model macrophage cell line. LPS-stimulated RAW 264.7 cells were exposed to HNE and the synthetic form of Hz, beta-hematin (BH), for 6 or 24 h. Microarray analysis identified alterations in gene expression induced by exposure to HNE and opsonized BH (fold change, > or = 1.8; p value, < or = 0.01). Patterns of gene expression were compared to changes induced by an opsonized control latex bead challenge in LPS-stimulated cells and revealed that the BH response was predominantly phagocytic. Ingenuity Pathway Analysis demonstrated that HNE mediated a short-term oxidative stress response and had a prolonged effect on the expression of genes associated with categories of "Cell Cycle", "Cellular Assembly and Organization", "DNA Replication, Recombination, and Repair", and "Cellular Development". Comparisons of expression changes caused by BH and HNE with those observed during malarial infection suggest that BH and HNE are involved in inflammatory response modulation, altered NF-kappaB signal transduction, extracellular matrix (ECM) degradation, and dyserythropoiesis. HNE exposure led to several significant steady-state expression changes including repressed chemokine (C-C motif) ligand 5 (Ccl5), indicative of dyserythropoiesis, and a severe matrix metalloproteinase 9 (Mmp9)/tissue inhibitor of metalloproteinase 1 (Timp1) imbalance in favor of ECM proteolysis.
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PMID:Comparative analysis of gene expression changes mediated by individual constituents of hemozoin. 1919 7

The biomarkers associated with coronary artery lesions (CAL) secondary to Kawasaki disease (KD) in Chinese children were investigated by using Meta-analysis. We searched documents published from January 1997 to December 2009 from medical electronic databases. According to inclusion and exclusion criteria, eligible full-text papers were identified. We conducted a comprehensive quantitative analysis by using Stata10.0 statistical software package to assess the heterogeneity among the documents, calculated the summary effect and analyze publication bias and sensitivity. A total of 92 documents and 16 biomarkers were identified. All documents were case-control studies, and included 2398 patients in CAL group and 5932 patients in non-CAL (NCAL) group. The Meta-analysis showed that the levels of platelet count, platelet hematocrit (PCT), neutrophils count, platelet distribution width (PDW), mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), cardiac troponin I (cTnI), and endothelin-1 (ET-1) in CAL group were significantly higher than those in NCAL group, and serum albumin (Alb) and hemoglobin (Hb) levels were significantly lower in CAL group (all P<0.05). White blood cell (WBC) count, serum sodium, matrix metalloproteinase 9 (MMP-9), total cholesterol (TC), hematocrit (HCT) and CD3+T lymphocytes percentage had no statistically significant difference between the two groups. In conclusion, our results indicated that the 10 biomarkers including platelet count, neutrophils count, PCT, PDW, MPV, ESR, cTnI, ET-1, Alb and Hb were associated with CAL, and may be involved in the pathogenesis of CAL. The biomarkers of WBC count, serum sodium, MMP-9, TC, HCT, and CD3+T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD.
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PMID:A meta-analysis of the biomarkers associated with coronary artery lesions secondary to Kawasaki disease in Chinese children. 2203 66

Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment.
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PMID:Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome. 2687 41