Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct morphological patterns of cell death have been recognized, termed necrosis and apoptosis. Apoptosis, or programmed cell death, occurs in both physiological and pathological conditions. It arises due to an elevation of cytosolic free calcium concentration resulting in activation of a nuclear endonuclease. Activated endonuclease produces oligonucleosome-length DNA fragments. This DNA cleavage can directly precipitate cell death. Both glucocorticoids and TCDD may induce apoptosis by production of a heat labile factor that mediates calcium influx whereas tributyltin causes the opening of calcium channels. Evidence that perturbation in calcium homeostasis is an important event in cell necrosis is becoming increasingly persuasive, but the events that propagate the lesion are still unclear. Despite evidence for cytoskeletal disruption, activation of degradative enzymes such as proteases and phospholipase A2 and stimulation of other enzymes such as poly (ADP-ribose) polymerase, the exact role that these play in cell killing is not resolved. Indeed, recently the radical dichotomy between apoptosis and necrotic cell death has come into question. It is clear that further work is required to determine the role played by some elements of the apoptotic process in chemically induced cell death.
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PMID:Mechanisms of cell death. 192 63

Ultraviolet light can affect the immune system locally as well as systemically leading to an impaired resistance to neoplastic cells and/or infections. Prior to the biological effect, UVB must be absorbed by a chromophore in the skin where it will give a signal that can lead to an altered immune response in the skin or elsewhere. These altered immune responses may be constituted by alteration in among others: cytokine profile, growth factors and costimulatory signals. Several hypotheses about the identity of the photoreceptor have been put forward. One photoreceptor in the skin is urocanic acid (UCA), that can isomerize from the trans- to the cis-isomer. The cis-isomer has immunosuppressive properties. Another photoreceptor is DNA that also efficiently absorbs UV wavelengths. After absorption the structure of the DNA molecule is altered. This alteration might lead to gene activation responsible for the immunotoxic outcome (altered gene expression). It has been demonstrated that the formation of DNA photoproducts by UV light is associated with the activation of many genes. Several studies indicate that UV-induced DNA damage, in the form of cyclobutyl pyrimidine dimers plays a role in UV-induced suppression of the immune system locally as well as systemically. In mice that were injected with liposomes containing the excision repair enzyme T4 endonuclease UVB-induced dimers were removed more efficiently as compared to control mice. In these mice UV-induced immunosuppression was prevented. Pilot studies by Kripke et al. indicated that the release of IL-IO and TNF alpha that are both induced by DNA damage might be involved. In preliminary studies with mice that were deficient with respect to DNA repair lower doses of UV were needed for the induction of immunosuppression as compared to their normal littermates. These studies indicate that altered gene expression plays a pivotal role in UVB-induced immunosuppression. In addition to a role for UCA and DNA in UV-induced immunosuppression it is postulated recently that signal transduction (EGF-receptor mediated upregulation of phospholipase A2) and transcription factors (NF kappa B, p91) are involved in UV-induced immunomodulation.
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PMID:Molecular aspects of UVB-induced immunosuppression. 907 98

Uteroglobin (UG) is a multifunctional protein with anti-inflammatory/immunomodulatory properties. The UG gene is located on the long arm of chromosome 11 (11q12.3-q13.1) in a region linked to some immune disorders. A guanine-adenine substitution at position 38 (A38G) has been found in the noncoding region of exon 1 that is significantly correlated with an increased risk of developing immune-mediated diseases. Recently an experimental model of UG knockout mice showed that in mice, UG deficiency causes severe glomerulopathy with mesangial deposition of IgA-fibronectin complexes. To detect the presence of polymorphisms in the UG coding sequence, the DNA of 109 patients with IgA nephropathy (IgAN), and 32 patients with systemic lupus erythematosus (SLE) were tested for the nucleotide sequence of all three UG exons by heteroduplex analysis. We detected heterozygous DNA only for exon 1 due to the A38G substitution, as confirmed by sequencing. We tested for A38G polymorphism, by restriction endonuclease digestion (Sau96I), both in SLE patients and in IgAN patients. Twenty patients with either membranous nephropathy (12) or focal and segmental glomerular sclerosis and 120 healthy subjects served as controls. Compared with both healthy controls and non-IgA control patients, the frequency of the 38A allele was significantly higher in SLE patients (38 of 64 alleles versus 89 of 240 alleles, p = 0.002, and versus 7 of 40 alleles, p < 0.001). IgAN patients showed an allelic distribution similar to both control groups. A subgroup of 18 IgAN patients undergoing renal replacement therapy because of end-stage renal disease showed a significant increase in 38A allele frequency (5 of 36 38G alleles versus 31 of 36 38A alleles, p < 0.001). UG is an immunomodulatory agent that is able to (a) inhibit the activity of several phospholipase A2 (PLA2s), (b) interfere with the function of both neutrophils and monocytes, and (c) prevent immune recognition, perhaps by masking surface antigens. This could account for the role this molecule plays in SLE. The A38G polymorphism is located within a region corresponding to the rat minimal promoter that proved to be important in the transcriptional regulation of UG. Although the significance of any alterations in the UG exon 1 noncoding region in humans has yet to be clarified, initial evidence suggests that it may alter the control of immune response and of inflammation.
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PMID:Polymorphism of the uteroglobin gene in systemic lupus erythematosus and IgA nephropathy. 1200 94

We report a method for detection of recurring side-chain patterns (DRESPAT) using an unbiased and automated graph theoretic approach. We first list all structural patterns as sub-graphs where the protein is represented as a graph. The patterns from proteins are compared pair-wise to detect patterns common to a protein pair based on content and geometry criteria. The recurring pattern is then detected using an automated search algorithm from the all-against-all pair-wise comparison data of proteins. Intra-protein pattern comparison data are used to enable detection of patterns recurring within a protein. A method has been proposed for empirical calculation of statistical significance of recurring pattern. The method was tested on 17 protein sets of varying size, composed of non-redundant representatives from SCOP superfamilies. Recurring patterns in serine proteases, cysteine proteases, lipases, cupredoxin, ferredoxin, ferritin, cytochrome c, aspartoyl proteases, peroxidases, phospholipase A2, endonuclease, SH3 domain, EF-hand and lectins show additional residues conserved in the vicinity of the known functional sites. On the basis of the recurring patterns in ferritin, EF-hand and lectins, we could separate proteins or domains that are structurally similar yet different in metal ion-binding characteristics. In addition, novel recurring patterns were observed in glutathione-S-transferase, phospholipase A2 and ferredoxin with potential structural/functional roles. The results are discussed in relation to the known functional sites in each family. Between 2000 and 50,000 patterns were enumerated from each protein with between ten and 500 patterns detected as common to an evolutionarily related protein pair. Our results show that unbiased extraction of functional site pattern is not feasible from an evolutionarily related protein pair but is feasible from protein sets comprising five or more proteins. The DRESPAT method does not require a user-defined pattern, size or location of the pattern and therefore, has the potential to uncover new functional sites in protein families.
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PMID:Functional sites in protein families uncovered via an objective and automated graph theoretic approach. 1258 52