Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Termites have an important role in the cycling of carbon and trace elements in the biosphere through their degradation of wood, grasses and humus. Glutathione transferases (GSTs) are detoxication enzymes found in all organisms; GSTs are known to protect insects from the toxic effects of plant chemicals and pesticides. The activities and characteristics of termite GSTs were investigated in three Australian termite families. Multiple GST isozymes were purified from whole body preparations of the three termite species by affinity chromatography and subsequent chromatofocusing. Termite GSTs exhibited a broad range of activities toward model substrates but were most active with 1-chloro-2,4-dinitrobenzene. The pI values of termite GSTs ranged between 7.4 and 5.8, while the apparent molecular weights of subunits ranged between 25.9 and 27.7 kDa. The N-terminal sequence of a glutathione-binding protein that was purified from Mastotermes darwiniensis was similar to the N-terminal sequence of a streptococcal protein of unknown function previously implicated in glomerulonephritis in humans.
Insect Biochem Mol Biol 1996 Jun
PMID:Glutathione transferases and glutathione-binding proteins of termites: purification and characterisation. 896 70

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.
Res Commun Mol Pathol Pharmacol 1997 Feb
PMID:Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis. 909 Jul 49

Chromatin, a huge polymer of nucleosomes, has been implicated as an important target of autoantibodies in idiopathic and drug-induced lupus for decades, but the antigenicity of chromatin has only recently been dissected. IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, is present in the majority of patients with systemic lupus erythematosus, in > 90% of patients with lupus induced by procainamide and in individual patients with lupus induced by a variety of other drugs, but is not seen in people taking these medications who are clinically asymptomatic. Anti-[(H2A-H2B)-DNA] accounted for the bulk of the anti-chromatin activity in drug-induced lupus. The earliest detectable autoantibody in lupus-prone mice recognized similar epitopes in the (H2A-H2B)-DNA subnucleosome complex; as the immune response progressed, native DNA and other constituents of chromatin became antigenic. The importance of chromatin-reactive T cells in the anti-[(H2A-H2B)-DNA] response is suggested by the presence of somatic mutations in antibody VH and VL regions, their predominant IgG isotype and the similarity in kinetics of their production to that of conventional T cell dependent antigens. Together with the serologic data from human lupus-like disease, these results are consistent with chromatin being a common stimulant for both B and T cells. While chromatin-reactive antibodies are closely associated with systemic disease and have recently been implicated in glomerulonephritis in SLE, the absence of renal disease in drug-induced lupus indicates that additional abnormalities are required to manifest the serious pathogenic of anti-[(H2A-H2B)-DNA] antibodies.
Mol Biol Rep 1996
PMID:Autoantibody to the nucleosome subunit (H2A-H2B)-DNA is an early and ubiquitous feature of lupus-like conditions. 911 24

MRL/Mp-lpr/lpr mice develop a spontaneous lupus syndrome, including hypergammaglobulinemia, autoantibodies, glomerulonephritis, and lymphadenopathy. To investigate the role of lymphocytes subsets in the pathogenesis of disease, lupus-prone MRL mice deficient in alpha beta T cells, gamma delta T cells, or both were generated. Mice deficient in alpha beta T cells developed a partially penetrant lupus syndrome, characterized by lymphadenopathy, elevated levels of class-switched immunoglobulins, an increased incidence of antinuclear antibodies, and immune deposits in kidneys which progressed to renal insufficiency over time. In comparison to wild type animals, gamma delta T cell-deficient animals developed an accelerated and exacerbated disease phenotype, characterized by accelerated hypergammaglobulinemia and enhanced autoantibody production and mortality. Repertoire analysis of these latter animals identified polyclonal expansion (V beta) of alpha beta CD4+ B220-cells. Mice lacking both alpha beta and gamma delta T cells failed to generate class-switched autoantibodies and immune complex renal disease. First, these findings demonstrate that murine lupus in the setting of Fas-deficiency does not absolutely require the presence of alpha beta T cells, and they also suggest that a significant basis for MRL/lpr disease, including renal disease, involves alpha beta T cell-independent, gamma delta T cell dependent, polyreactive B cell autoimmunity, upon which alpha beta T cell-dependent mechanisms aggravate specific autoimmune responses. Second, these data indicate that gamma delta T cells partake in the regulation of systemic autoimmunity, presumably via their effects on alpha beta CD4+ B220-T cells that provide B cell help. Finally, these results demonstrate that MRL/lpr B cells, despite their intrinsic abnormalities, cannot per se cause tissue injury without T cell help.
Mol Biol Rep 1996
PMID:T cells in murine lupus: propagation and regulation of disease. 911 36

The endothelin peptide family consists of the 21 amino acid isoforms endothelin-1, endothelin-2, endothelin-3, and sarafotoxin (a snake venom). Endothelin-1 has been isolated from the supernatant of endothelial cells and has subsequently been shown to be the most potent vasoconstrictor known to date and to be positively inotropic. This review summarizes some of the current literature pertaining to circulatory and myocardial effects of endothelins. Exogenously administered endothelin-1 has been demonstrated to increase peripheral resistance and blood pressure in a dose-dependent manner. However, during the first minutes of intravenous administration endothelins also decrease peripheral resistance and blood pressure, presumably due to the release of vasodilatory compounds such as nitric oxide, prostacyclin, and atrial natriuretic peptide. Endothelins appear to be involved in the pathogenesis of salt-dependent and renovascular animal models of experimental hypertension. Although endothelins appear to contribute to basal vascular tone, the role of endothelins in the pathophysiology of human hypertension remains unclear. In addition, a role has been suggested for endothelins in specific vascular lesions and inflammatory conditions (e.g., restenosis after coronary angioplasty, atherosclerotic coronary lesions, acute myocardial infarction, and vasculitis, glomerulonephritis). Endothelins are positively inotropic peptides in cardiac myocyte and papillary muscle preparations. They have also been demonstrated to induce hypertrophy of cardiac myocyte and may play an important role in ventricular processes that lead to chronic cardiac failure. The pathophysiological relevance of the endothelin system in human disease states is elucidated using selective (ET[A]) and nonselective (ET[A/B]) inhibitors of the endothelin receptors.
J Mol Med (Berl)
PMID:Circulatory and myocardial effects of endothelin. 942 21

Interleukin-8 (IL-8) is a cytokine, which possesses both chemotactic and activating properties for neutrophils, lymphocytes and basophils. Various evidence has indicated IL-8 to be implicated in the pathophysiology of immune-mediated renal diseases. We thus examined the expression of IL-8 in renal diseases. We detected the expression of IL-8 both in mRNA and the protein levels in renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis. A significant correlation was found between the expression of IL-8 mRNA and the number of neutrophils in the glomerulus. We also found a negative correlation between the expression of IL-8 mRNA and creatinine clearance. Our study thus suggested IL-8 to be involved in the pathophysiology of proliferative glomerulonephritis.
Res Commun Mol Pathol Pharmacol 1998 Feb
PMID:Expression of interleukin-8 in human glomerulonephritis. 958 95

We measured the concentration of serum glycosaminoglycans (GAGs) in patients with glomerulonephritis, renal failure and on hemodialysis using the dye binding method. In glomerulonephritis, concentration of serum GAGs did not increase, and there was no correlation between serum and urinary GAGs. In patients with renal failure and hemodialysis, concentration of serum GAGs was significantly lower than in controls. Concentration of serum GAGs was correlated with concentration of serum albumin, which is an indicator of malnutrition in patients on hemodialysis. One month of hemodialysis did not affect the concentration of serum GAGs in patients with renal failure, but six months of hemodialysis increased the concentration of serum GAGs. These results suggest that matrix production is suppressed in renal failure with malnutrition.
Res Commun Mol Pathol Pharmacol 1998 Feb
PMID:Levels of serum glycosaminoglycans in renal failure. 958 96

We demonstrated activation of transcription factor AP-1 in rat nephrotoxic serum (NTS)-induced glomerulonephritis in a previous report. Here, we evaluate c-Jun N-terminal kinases (JNKs) activity to clarify the molecular mechanisms of AP-1 activation in nephritic glomeruli. Increased JNKs activity was detected in glomeruli isolated from NTS-treated rats. The kinetics of JNKs activation was similar to that of AP-1 activation. Phosphorylated c-Jun at Ser63, one of the target residues for JNK, was also detected in nephritic glomeruli. This is the first report demonstrating JNKs-mediated c-Jun/AP-1 activation in nephritic glomeruli. These results suggest an important role of the JNK-AP-1 signaling pathway in the pathogenesis of glomerulonephritis.
Biochem Mol Biol Int 1998 Jul
PMID:c-Jun N-terminal kinase-mediated AP-1 activation in experimental glomerulonephritis in rats. 971 8

Autoantibodies to MPO are associated with various forms of systemic vasculitis, including the renal limited form described as idiopathic crescentic glomerulonephritis. In vitro the antibodies are able to further activate primed neutrophils to the production of reactive oxygen species and the release of lysosomal enzymes. In vivo experimental studies in which an autoimmune response to MPO was induced in rats have demonstrated the in vivo potential of the autoantibodies to aggravate subclinical inflammatory lesions. In the right context, vasculitis and glomerulonephritis can ensue. Further studies are being directed to the precise characterization of autoimmune responses in order to obtain clues for the etiopathogenesis of the associated diseases.
J Mol Med (Berl) 1998 Sep
PMID:Autoantibodies to myeloperoxidase: clinical and pathophysiological significance. 976 46

Mice injected at birth with semiallogeneic spleen cells develop a host-versus-graft disease (HVGD) characterized by the polyclonal activation of donor B cells by alloreactive host CD4+ T cells, the production of autoantibodies (autoAb) and the development of an inmmunocomplex-mediated glomerulonephritis. It has been demonstrated that the recognition of MHC class II, but not class I or non MHC, alloantigens triggers the development of the autoimmune syndrome (AIS). The finding of different expression patterns of Ia molecules in different mouse strains, and a closed restriction of some immune responses to particular H-2 haplotypes, prompted us to analyze whether variations in the expressed MHC class II molecules modify the HVGD. First, newborn BALB/c mice received spleen cells from F1 hybrid mice obtained by mating BALB/c mice with several mouse strains differing in the H-2 haplotype. Second, spleen cells from different F1 mice were neonatally injected in mice of both parental strains. All groups of BALB/c mice injected with different combinations of F1 mice showed an HVGD with a very similar serological course. However, in some instances, duration was different when comparing both parental strains injected with spleen cells from the mutual F1 hybrids. These results suggest that host MHC, but not donor MHC haplotype may modulate the AIS associated with the induction of neonatal tolerance.
Int J Mol Med 1998 Feb
PMID:Host H-2 haplotype modulates the induction of host-versus-graft disease after the induction of neonatal tolerance to H-2 alloantigens. 985 47


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