Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, and cytotoxic effects. During bacterial infection of the bloodstream (sepsis), TNF-alpha induction by bacterial endotoxin is thought to be a major factor contributing to the cardiovascular collapse and critical organ failure that can develop. Despite antibiotic therapy, these consequences of sepsis continue to have a high mortality rate in humans. Here we describe a potent TNF antagonist, a TNF receptor (TNFR) immunoadhesin, constructed by gene fusion of the extracellular portion of human type 1 TNFR with the constant domains of human IgG heavy chain (TNFR-IgG). When expressed in transfected human cells, TNFR-IgG is secreted as a disulfide-bonded homodimer. Purified TNFR-IgG binds to both TNF-alpha and TNF-beta and exhibits 6- to 8-fold higher affinity for TNF-alpha than cell surface or soluble TNF receptors. In vitro, TNFR-IgG blocks completely the cytolytic effect of TNF-alpha or TNF-beta on actinomycin D-treated cells and is markedly more efficient than soluble TNFR (24-fold) or monoclonal anti-TNF-alpha antibodies (4-fold) in inhibiting TNF-alpha. In vitro, TNFR-IgG prevents endotoxin-induced lethality in mice when given 0.5 hr prior to endotoxin and provides significant protection when given up to 1 hr after endotoxin challenge. These results confirm the importance of TNF-alpha in the pathogenesis of septic shock and suggest a clinical potential for TNFR-IgG as a preventive and therapeutic treatment in sepsis.
 ...
PMID:Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. 166 Jan 40

Cells of the macrophage lineage express a peculiar surface receptor for extracellular ATP, designated P2Z/P2X7 purinergic receptor, that induces pore formation and collapse of the plasma membrane potential. Although the function of the P2Z receptor is largely unknown, accumulating evidence implicates its role in cell signaling and immune reactions. Here, we investigated the effect of P2Z receptor ligation on the activation of NF-kappaB, a transcription factor controlling cytokine expression and apoptosis. Exposure of microglial cells to ATP but not other nucleotides resulted in potent NF-kappaB activation. This effect was specifically mediated by the P2Z receptor, because selective receptor antagonists prevented NF-kappaB activation. NF-kappaB activation required reactive oxygen intermediates and proteases of the caspase family, because it was abolished by antioxidants and specific protease inhibitors. The subunit composition of the ATP-induced NF- kappaB-DNA complex was rather unusual. Whereas exposure to LPS-induced prototypical NF-kappaB p50 homo- and p65 (RelA)/p50 heterodimers, ATP stimulation resulted in the sole appearance of a p65 homodimer. This is the first demonstration that a certain stimulus activates a particular NF-kappaB subunit. Because different NF-kappaB complexes exhibit distinct transcriptional and DNA-binding activities, ATP may control the expression of a subset of NF-kappaB target genes distinct from those activated by classical proinflammatory mediators.
 ...
PMID:Extracellular ATP activates transcription factor NF-kappaB through the P2Z purinoreceptor by selectively targeting NF-kappaB p65. 941 59

The electron-transfer (ET) reaction between Fe(CN)6(4-) and copper zinc superoxide dismutase (CuZn-SOD) occurs at the active site of the enzyme. The ET parameters which are sensitive to the denaturation have been used to determine the conformational changes of the active site induced by guanidine hydrochloride and thermal denaturation. The decreases of ET rates for all the denatured enzyme samples reflect the collapse of the active cavity of enzyme in the unfolding processes. The interesting changes of ET amplitude for the enzyme denatured at different pH values suggest that electrostatic interaction plays an important role in the conformational changes of active site. From the results of the kinetic analyses, it is concluded that the conformational changes of the active site are parallel with the inactivation.
 ...
PMID:Conformational changes of active site of copper zinc superoxide dismutase can be detected sensitively by electron-transfer reaction. 977 44

Results obtained with graded concentrations of NaCl (20-200 m M) show decrease in the chlorophyll 'a' contents of Anabaena with increasing concentration of NaCl except at extremely low concentration of NaCl (5-20 m M). The rate of Hill activity and oxygen evolution are found to be stimulated by lower concentrations of NaCl, but not at higher concentrations of NaCl. Results have demonstrated that the O(2) evolution process is relatively more sensitive to NaCl stress than the Hill activity. Further, the results show NaCl induced an increase in the rate of RNO bleaching and loss of total thiol (-SH) contents. Taken together, these results suggest a NaCl-induced general oxidative stress. Results on the effect of oxygen radical quenchers reveal a predominant role of singlet oxygen in the NaCl-induced general oxidative stress as evident from a higher quenching effect of sodium azide than formate and histidine on the rate of RNO bleaching in Anabaena cells. However, the rate of lipid peroxidation and SOD activity show a declining pattern in response to increasing concentrations of NaCl. There is the possibility of a NaCl-induced decrease in the rate of lipid peroxidation when the SOD activity is also lower. But the NaCl-induced decline in the SOD activity does suggest that symptoms of general oxidative stress at elevated levels of NaCl are apparently owing to collapse of intracellular defense of the cells against the toxic oxygen radicals, not because of the higher rate of photosynthetic activity.
 ...
PMID:NaCl-induced oxidative damage in the cyanobacterium Anabaena doliolum. 1200 Sep 91

Peroxisomes, being one of the main organelles where reactive oxygen species (ROS) are both generated and detoxified, have been suggested to be instrumental in redox-mediated plant cell defence against oxidative stress. We studied the involvement of tomato (Lycopersicon esculentum Mill.) leaf peroxisomes in defence response to oxidative stress generated upon Botrytis cinerea Pers. infection. The peroxisomal antioxidant potential expressed as superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) and glutathione peroxidase (GSH-Px, EC 1.11.1.19) as well as the ascorbate-glutathione (AA-GSH) cycle activities was monitored. The initial infection-induced increase in SOD, CAT and GSH-Px indicating antioxidant defence activation was followed by a progressive inhibition concomitant with disease symptom development. Likewise, the activities of AA-GSH cycle enzymes: ascorbate peroxidase (APX, EC 1.11.1.11), monodehydroascorbate reductase (MDHAR, EC 1.6.5.4), dehydroascorbate reductase (DHAR, EC 1.8.5.1) and glutathione reductase (GR, EC 1.6.4.2) as well as ascorbate and glutathione concentrations and redox ratios were significantly decreased. However, the rate and timing of these events differed. Our results indicate that B. cinerea triggers significant changes in the peroxisomal antioxidant system leading to a collapse of the protective mechanism at advanced stage of infection. These changes appear to be partly the effect of pathogen-promoted leaf senescence.
 ...
PMID:Fungal pathogen-induced changes in the antioxidant systems of leaf peroxisomes from infected tomato plants. 1584 61

Combined radiotherapy and chemotherapy have represented major advance in the therapeutic management of cancer therapy. Anthracycline antineoplastic agents are limited by a high incidence of severe and usually irreversible cardiac toxicity, the cause of which remains controversial. When the primary cardiomyocytes isolated from neonatal rats were preirradiated by gamma-ray, the cells were highly resistant to adriamycin-induced apoptosis. This study shows that irradiation inhibited apoptosis by enhancing Bcl-2, attenuating Bax induction, and preventing collapse of mitochondrial membrane potential (delta psi), cytochrome c release into cytoplasm and caspase-3, -6 and -9 activations. In addition, the preirradiation stimulated the activity of manganese-superoxide dismutase (Mn-SOD) and the expression of Mn-SOD mRNA and protein. Adriamycin decreased Mn-SOD activity but did not change the activity of copper/zinc (Cu/Zn)-SOD under either pre- or nonirradiated condition. Phosphothioate-linked antisense against Mn-SOD, which specifically knocked down the activity of Mn-SOD but not that of Cu/Zn-SOD, reversed irradiation-induced protective effect in adriamycin-exposed cardiomyocytes. These data suggest that the irradiation-induced expression of Mn-SOD plays an important role in irradiation-mediated protection in adriamycin-exposed rat ventricular cardiomyocytes.
 ...
PMID:Radiation protects adriamycin-induced apoptosis. 1611 6

Proteins fold into a well-defined structure as a result of the collapse of the polypeptide chain, while transient protein-complex formation mainly is a result of binding of two folded individual monomers. Therefore, a protein-protein interface does not resemble the core of monomeric proteins, but has a more polar nature. Here, we address the question of whether the physico-chemical characteristics of intraprotein versus interprotein bonds differ, or whether interfaces are different from folded monomers only in the preference for certain types of interactions. To address this question we assembled a high resolution, nonredundant, protein-protein interaction database consisting of 1374 homodimer and 572 heterodimer complexes, and compared the physico-chemical properties of these interactions between protein interfaces and monomers. We performed extensive statistical analysis of geometrical properties of interatomic interactions of different types: hydrogen bonds, electrostatic interactions, and aromatic interactions. Our study clearly shows that there is no significant difference in the chemistry, geometry, or packing density of individual interactions between interfaces and monomeric structures. However, the distribution of different bonds differs. For example, side-chain-side-chain interactions constitute over 62% of all interprotein interactions, while they make up only 36% of the bonds stabilizing a protein structure. As on average, properties of backbone interactions are different from those of side chains, a quantitative difference is observed. Our findings clearly show that the same knowledge-based potential can be used for protein-binding sites as for protein structures. However, one has to keep in mind the different architecture of the interfaces and their unique bond preference.
 ...
PMID:Similar chemistry, but different bond preferences in inter versus intra-protein interactions. 1826 Jan 1

Different defense mechanisms of three spring wheat (Triticum aestivum L.) varieties were studied by withholding watering in well-watered pots to gradually increase water deficit of plants grown in containers. The strategies of plant adaptation were divided into three phases according to the severity of drought: first, a positive defense phase that started from commencement of non-hydraulic root-sourced signals (nHRS) and ended at onset of hydraulic root-sourced signals (HRS)--the plant responded to imminent drought by decreasing stomatal aperture to lessen water loss and no membrane injury occurred. The second defense phase occurred between the onset of HRS and temporary wilting (TW), characterized by enhancement of reactive oxygen species (ROS), marked enzyme activity and increased MDA content. Mild lipid membrane peroxidation came mainly from a dynamic imbalance between free radical production and enzymatic defense reaction, which indicated that injury by ROS had not been completely repaired by increasing enzymatic activity. The third defense phase was from TW to permanent wilting (PW), the synthesis of SOD and CAT during TW could not deal with the collapse of antioxidant enzymes, and SOD and CAT activities began to decrease, which caused the excessive ROS production and thus serious membrane lipid peroxidation. The defense strategies to drought are similar among the varieties, but modern varieties LC8275 and GY602 bred after 1975 had relatively higher defense levels at all three defense phases, which suggest that modern varieties are more resistant than old ones, and artificial selection would lead to a different direction in evolution from natural selection.
 ...
PMID:Defense strategy of old and modern spring wheat varieties during soil drying. 1945 98

Chronic exposure to copper induces hepatocellular apoptosis with greater injury in the periportal region compared to the perivenous region. Here we have identified the factors responsible for the development of regional damage in the liver under in vivo conditions. Enhanced production of reactive oxygen species (ROS) with predominance of superoxide radical (O(2)(-)) indicates the contribution of redox imbalance in the process. This may be linked with copper catalyzed oxidation of GSH to GSSG resulting in the generation of O(2)(-). Downregulation of Cu-Zn SOD in consequence of the degradation of this enzyme, causes decreased dismutation of O(2)(-), that further contributes to the enhanced level of O(2)(-) in the periportal region. Decreased functioning of Mn SOD activity, reduction in mitochondrial thiol/disulphide ratio and generation of O(2)(-) were much higher in the mitochondria from periportal region, which point to the involvement of this organelle in the regional hepatotoxicity observed during copper exposure. This was supported by copper-mediated enhanced mitochondrial dysfunction as evident from ATP depletion, collapse of mitochondrial membrane potential (MMP) and induction of mitochondrial permeability transition (MPT). Results suggest the active participation of O(2)(-) in inducing mitochondrial dysfunction preferentially in the periportal region that eventually leads to the development of hepatotoxicity due to copper exposure under in vivo condition.
 ...
PMID:Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats. 1971 84

Application of simultaneous low pH (pH 3.5) and low water activity (a(w)=0.9; 2.5M NaCl) conditions to Listeria monocytogenes strains ScottA and FW03/0035, and growth permissive temperatures from 25 degrees C up to 45 degrees C result in increasingly accelerated inactivation rates. This phenomenon was related to i) increased cell permeability as suggested by ethidium homodimer-1 uptake and ii) de-energization as indicated by rapidly reduced ATP basal levels. Enrichment-based recovery experiments indicated that the stress conditions eventually lead to complete loss of reproductive capacity, possibly corresponding to an irreversible collapse of pH homeostasis. Transcriptomic analyses were used to obtain further insights into the physiology of the inactivation process occurring at 25 degrees C where inactivation times were more prolonged. QPCR, mRNA decay and microarray experiments revealed transcripts of tufA and other genes become substantially more stable during inactivation resulting from exposure to combined low pH/a(w) and from non-growth permissive temperature exposure. Genes that appear to be important for initial survival of combined low pH/a(w) were delineated by K-means clustering of expression data and included an overrepresentation of SigB-activated genes, the overall response of which fades with increasing time of inactivation exposure.
 ...
PMID:Physiological aspects of Listeria monocytogenes during inactivation accelerated by mild temperatures and otherwise non-growth permissive acidic and hyperosmotic conditions. 2055 35


1 2 3 Next >>