Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase A2 [EC 3.1.1.4] treatment of pig kidney Na+,K(+)-ATPase [EC 3.6.1.3] labeled with fluorescence probes at the alpha-chain reduced the extent of the fluorescence intensity change of an N-[p-(2-benzimidazolyl)phenyl]maleimide (BIPM) probe at Cys-964 to below one-third of the control level accompanying the accumulation of phosphoenzymes. However, it only induced a slight decrease in that of a fluorescence isothiocyanate (FITC) probe at Lys-501 with a large decrease in the rate of change. The addition of phosphatidylserine (PS) or phosphatidylinositol (PI) to the phospholipase-treated BIPM-FITC-labeled enzyme increased the rate of the FITC fluorescence change. Phospholipase treatment of the BIPM-enzyme greatly reduced the Na+,K(+)-ATPase activity. The addition of PS or PI to the treated enzyme induced reactivation. These data and others suggest that Cys-964 and Glu-953 (Rb+ protectable dicyclohexyl carbodiimide binding site) are located in the vicinity of the surface area of the enzyme where hydrocarbon chains of phospholipids are present, and conserved H-bonding amino acids, Thr-955 and Ser-962, are located rather near the center of a domain forming a cation binding route or cage with other hydrophobic transmembrane segments. These data may indicate that the interaction between the BIPM probe and the hydrocarbon chains of phospholipids changes in such a way as to sense the change in the binding state of various ligands accompanying the sequential appearance of reaction intermediates of the enzyme.
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PMID:Different susceptibility to phospholipase A2 treatment of the fluorescence intensity changes in the vicinity of Cys-964 and Lys-501 in the alpha-chain of probe-labeled Na+,K(+)-ATPase. 805 57

One potential strategy for the control of malaria and other vector-borne diseases is the introduction into wild vector populations of genetic constructs that reduce vectorial capacity. An important caveat of this approach is that the genetic construct should have minimal fitness cost to the transformed vector. Previously, we produced transgenic Anopheles stephensi expressing either of two effector genes, a tetramer of the SM1 dodecapeptide or the phospholipase A2 gene (PLA2) from honeybee venom. Mosquitoes carrying either of these transgenes were impaired for Plasmodium berghei transmission. We have investigated the role of two effector genes for malaria parasite blockage in terms of the fitness imposed to the mosquito vector that expresses either molecule. By measuring mosquito survival, fecundity, fertility, and by running population cage experiments, we found that mosquitoes transformed with the SM1 construct showed no significant reduction in these fitness parameters relative to nontransgenic controls. The PLA2 transgenics, however, had reduced fitness that seemed to be independent of the insertion site of the transgene. We conclude that the fitness load imposed by refractory gene(s)-expressing mosquitoes depends on the effect of the transgenic protein produced in that mosquito. These results have important implications for implementation of malaria control via genetic modification of mosquitoes.
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PMID:Fitness of anopheline mosquitoes expressing transgenes that inhibit Plasmodium development. 1508 52

The electrophile Ca(2+) is an essential multifunctional co-factor in the phospholipase A(2) mediated hydrolysis of phospholipids. Crystal structures of an acidic phospholipase A(2) from the venom of Bothrops jararacussu have been determined both in the Ca(2+) free and bound states at 0.97 and 1.60 A resolutions, respectively. In the Ca(2+) bound state, the Ca(2+) ion is penta-coordinated by a distorted pyramidal cage of oxygen and nitrogen atoms that is significantly different to that observed in structures of other Group I/II phospholipases A(2). In the absence of Ca(2+), a water molecule occupies the position of the Ca(2+) ion and the side chain of Asp49 and the calcium-binding loop adopts a different conformation.
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PMID:Insights into metal ion binding in phospholipases A2: ultra high-resolution crystal structures of an acidic phospholipase A2 in the Ca2+ free and bound states. 1637 74

The differential anticarcinogenic activity of conjugated linoleic acid (CLA) isomers, including c9,t11-CLA, t10,c12-CLA, and t,t-CLA, was examined in a mouse forestomach carcinogenesis regimen induced by benzo(a)pyrene (BP). Female ICR mice (6-7 weeks of age, 26 +/- 1 g) were divided into six groups (30 mice/group, 5 mice/cage): control, linoleic acid, CLA, c9,t11-CLA, t10,c12-CLA, and t,t-CLA. Each mouse was orally given 0.1 mL of sample and 0.1 mL of olive oil on Monday and Wednesday and BP (2 mg in 0.2 mL of olive oil) on Friday. This cycle was repeated four times. Twenty-three weeks later, the experiment was terminated for tumor analysis. t,t-CLA significantly reduced (p < 0.05) both tumor number and tumor size per mouse, relative to CLA and c9,t11-CLA, but similar to t10,c12-CLA. Reduction in tumor incidence by t,t-CLA (84.6%) was similar to that by CLA, c9,t11-CLA, and t10,c12-CLA, but it was significantly reduced (p < 0.05), relative to 100% linoleic acid and control. t,t-CLA elevated the apoptotic index to 35%, relative to 23% for CLA, 21% for c9,t11-CLA, 29% for t10,c12-CLA, 7% for linoleic acid, and 4% for control. t,t-CLA up-regulated the expression of the Bax gene and activated caspase-3 enzymes but down-regulated expression of the Bcl-2 gene. Cytosolic phospholipase A(2) activity was not affected by the CLA isomers tested. These results suggest that t,t-CLA has superior anticarcinogenic potential on BP-induced mouse forestomach neoplasia to CLA, c9,t11-CLA, and t10,c12-CLA, via the induction of apoptosis through mitochondrial dysfunction.
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PMID:Differential inhibitory effects of conjugated linoleic acid isomers on mouse forestomach neoplasia induced by benzo(a)pyrene. 2015 12

Blood transfusions temporarily improve the physical state of the patient but exert widespread effects on immune and non-immune systems. Perioperative allogeneic blood transfusions (ABT) are associated with various risks, including coagulopathy, incompatibility, transmission of infectious agents, and allergic reactions. Nevertheless, little is known about the global metabolic alterations that reflect the possible reactions of blood transfusions. In this study, we investigated metabolite changes generated by ABT in a rat model using metabolomics technology. To further profile the "metabolome" after blood transfusions, we used both liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry and gas chromatography-mass spectrometry. ABT promoted a stimulatory microenvironment associated with a relative increase in glucose transporter 1/4 (GLUT1/GLUT4) expression. Supporting this result, glucose metabolism-related enzyme IRS1 and interleukin-6 (IL-6) were abnormally expressed, and levels of lysophosphatidylcholine (LysoPC) and its related enzyme phospholipase A2 (PLA2) were significantly altered in allogeneic groups compared to those in autologous groups. Finally, amino acid metabolism was also altered following ABT. Taken together, our results show a difference between autologous and allogeneic blood transfusions and demonstrate correlations with cancer-associated metabolic changes. Our data provide endogenous information for a better understanding of blood transfusion reactions.
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PMID:Metabolomics Approach Based on Multivariate Techniques for Blood Transfusion Reactions. 3074 55