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991.
The plasma concentration of secretin was measured during a 5-day military training course comprising prolonged physical exercise (35% of max O2 uptake), severe caloric deficiency (approx. 35700 kJ/24 h) and sleep deprivation (only 2 h of sleep as a total during 5 days). 24 subjects were divided into 3 groups, one group was compensated for the caloric deficiency and another group was partly compensated for the sleep deprivation. The results showed that the fasting plasma secretin increased 3–6-fold (from 1.8–3.7 to 13.3–19.1 pmol/l) during the course with small differences in increase between the groups. Ingestion of a mixed meal reduced the fasting plasma secretin by about 40% during the course, while oral glucose reduced the plasma secretin to the concentrations found in the control experiment.The study shows that plasma secretin is increased when man is exposed to prolonged multifactorial stress. Additional food or sleep appears to have small influence on the fasting plasma secretin, but after giving a meal or oral glucose solution the plasma secretin decreases rapidly. 相似文献
992.
Yoshinobu Ohira Jack Hegenauer Paul Saltman V. Reggie Edgerton 《Biological trace element research》1982,4(1):45-56
Iron-deficiency anemia leads directly to both reduced hemoglobin levels and work performance in humans and experimental animals.
In an attempt to observe a direct link between work performance and insufficient iron at the cellular level, we produced severe
iron deficiency in female weanling Sprague-Dawley rats following five weeks on a low-iron diet. Deficient rats were compared
with normal animals to observe major changes in hematological parameters, body weight, and growth of certain organs and tissues.
The overall growth of iron-deficient animals was approximately 50% of normal. The ratio of organ weight: body weight increased
in heart, liver, spleen, kidney, brain, and soleus muscle in response to iron deficiency. Further, mitochondria from heart
and red muscle retained their iron more effectively under the stress of iron deficiency than mitochondria from liver and spleen.
Metabolism of iron in normal and depleted tissue was measured using tracer amounts of59Fe administered orally. As expected, there was greater uptake of tracer iron by iron-deficient animals. The major organ of
iron accumulation was the spleen, but significant amounts of isotope were also localized in heart and brain. In all muscle
tissue examined the59Fe preferentially entered the mitochondria. Enhanced mitochondrial uptake of iron prior to any detectable change in the hemoglobin
level in experimental animals may be indicative of nonhemoglobin related biochemical changes and/or decrements in work capacity. 相似文献
993.
The effects of neonatal undernutrition and postweaning protein deficiency on the content and lipid composition of gray and
white matter of 63 days old rat brain have been studied. The concentrations of different lipids remain the same, but the relative
proportion of gray and white matter changes thus reflecting the differences in the concentration of whole brain lipids. 相似文献
994.
The bacteriocin butyricin 7423 inhibited the activity of the membrane H+-ATPase (BF0, F1) of vegetative cells of Clostridium pasteurianum but not that of its soluble BF1 component. In vitro studies with the H+-ATPases of mutant strains selected for diminished sensitivity (a) to butyricin 7423 and (b) to dicyclohexylcarbodi-imide, confirmed that butyricin 7423 interacts with the BF0 component of this enzyme complex. Even so, certain other mutant strains displaying decreased sensitivity to butyricin 7423 possessed H+-ATPases which in vitro showed undiminished sensitivity to inhibition by the bacteriocin. Furthermore, from the changes in intracellular ATP concentration and in the rates and net extent of efflux of intracellular 86Rb+ ions that were provoked by exposure of the parent and several of the mutant strains to butyricin 7423, it was concluded that its primary bactericidal action was not attributable to stoichiometric inhibition of the membrane H+-ATPase. High extracellular concentrations of K+ ions enabled Cl. pasteurianum to survive exposure to low concentrations of this membrane-active bacteriocin.Non-standard abbreviations H+-ATPase
proton translocating adenosine 5-triphosphatase (EC 3.6.1.3)
- DCCD
dicyclohexylcarbodiimide 相似文献
995.
Uptake of Adenosine by Isolated Rat Brain Capillaries 总被引:5,自引:4,他引:1
Abstract: Adenosine uptake by isolated rat brain capillaries is a carrier-mediated, temperature- and pH-sensitive process. The K m value for adenosine uptake is 4.74 μ m and the V max is 21.7 picomol/mg protein/10 min. This is a high-affinity uptake system that can be cross-inhibited by several nucleosides and by the adenosine analogs tubercidin and 5'-deoxyadenosine. The uptake is very sensitive to inhibition by papaverine, hexobendine, and dipyridamole. These results confirm the existence of a nucleoside transport system associated with the blood-brain barrier observed during in vivo studies. 相似文献
996.
Adh4, a member of the mouse alcohol dehydrogenase (ADH) gene family, encodes an enzyme that functions in vitro as a retinol dehydrogenase in the conversion of retinol to retinoic acid, an important developmental signaling molecule. To explore the role of Adh4 in retinoid signaling in vivo, gene targeting was used to create a null mutation at the Adh4 locus. Homozygous Adh4 mutant mice were viable and fertile and demonstrated no obvious defects when maintained on a standard mouse diet. However, when subjected to vitamin A deficiency during gestation, Adh4 mutant mice demonstrated a higher number of stillbirths than did wild‐type mice. The proportion of liveborn second generation vitamin A‐deficient newborn mice was only 15% for Adh4 mutant mice but 49% for wild‐type mice. After retinol administration to vitamin A‐deficient dams in order to rescue embryonic development, Adh4 mutant mice demonstrated a higher resorption rate at stage E12.5 (69%), compared with wild‐type mice (30%). The relative ability of Adh4 mutant and wild‐type mice to metabolize retinol to retinoic acid was measured after administration of a 100‐mg/kg dose of retinol. Whereas kidney retinoic acid levels were below the level of detection in all vehicle‐treated mice (<1 pmol/g), retinol treatment resulted in very high kidney retinoic acid levels in wild‐type mice (273 pmol/g) but 8‐fold lower levels in Adh4 mutant mice (32 pmol/g), indicating a defect in metabolism of retinol to retinoic acid. These findings demonstrate that another retinol dehydrogenase can compensate for a lack of Adh4 when vitamin A is sufficient, but that Adh4 helps optimize retinol utilization under conditions of both retinol deficiency and excess. Dev. Genet. 25:1–10, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
997.
The A3 adenosine receptor (AR) is emerging as an attractive drug target. Antagonists are proposed for the potential treatment of glaucoma and asthma. However, currently available A3AR antagonists are potent in human and some large animals, but weak or inactive in mouse and rat. In this study, we re-synthesized a previously reported A3AR antagonist, DPTN, and evaluated its affinity and selectivity at human, mouse, and rat ARs. We showed that DPTN, indeed, is a potent A3AR antagonist for all three species tested, albeit a little less selective for mouse and rat A3AR in comparison to the human A3AR. DPTN’s Ki values at respective A1, A2A, A2B, and A3 receptors were (nM) 162, 121, 230, and 1.65 (human); 411, 830, 189, and 9.61 (mouse); and 333, 1147, 163, and 8.53 (rat). Its antagonist activity at both human and mouse A3ARs was confirmed in a cyclic AMP functional assay. Considering controversial use of currently commercially available A3AR antagonists in rats and mice, we also re-examined other commonly used and selective A3AR antagonists under the same experimental conditions. The Ki values of MRS1523 were shown to be 43.9, 349, and 216 nM at human, mouse, and rat A3ARs, respectively. MRS1191 and MRS1334 showed incomplete inhibition of [125I]I-AB-MECA binding to mouse and rat A3ARs, while potent human A3AR antagonists, MRS1220, MRE3008F20, PSB10, PSB-11, and VUF5574 were largely inactive. Thus, we demonstrated that DPTN and MRS1523 are among the only validated A3AR antagonists that can be possibly used (at an appropriate concentration) in mouse or rat to confirm an A3AR-related mechanism or function.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11302-021-09823-5. 相似文献
998.
999.
Adriana Ann Garcia Irimpan I. Mathews Naoki Horikoshi Tsutomu Matsui Manat Kaur Soichi Wakatsuki Daria Mochly-Rosen 《The Journal of biological chemistry》2022,298(3)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic trait that can cause hemolytic anemia. To date, over 150 nonsynonymous mutations have been identified in G6PD, with pathogenic mutations clustering near the dimer and/or tetramer interface and the allosteric NADP+-binding site. Recently, our lab identified a small molecule that activates G6PD variants by stabilizing the allosteric NADP+ and dimer complex, suggesting therapeutics that target these regions may improve structural defects. Here, we elucidated the connection between allosteric NADP+ binding, oligomerization, and pathogenicity to determine whether oligomer stabilization can be used as a therapeutic strategy for G6PD deficiency (G6PDdef). We first solved the crystal structure for G6PDK403Q, a mutant that mimics the physiological acetylation of wild-type G6PD in erythrocytes and demonstrated that loss of allosteric NADP+ binding induces conformational changes in the dimer. These structural changes prevent tetramerization, are unique to Class I variants (the most severe form of G6PDdef), and cause the deactivation and destabilization of G6PD. We also introduced nonnative cysteines at the oligomer interfaces and found that the tetramer complex is more catalytically active and stable than the dimer. Furthermore, stabilizing the dimer and tetramer improved protein stability in clinical variants, regardless of clinical classification, with tetramerization also improving the activity of G6PDK403Q and Class I variants. These findings were validated using enzyme activity and thermostability assays, analytical size-exclusion chromatography (SEC), and SEC coupled with small-angle X-ray scattering (SEC-SAXS). Taken together, our findings suggest a potential therapeutic strategy for G6PDdef and provide a foundation for future drug discovery efforts. 相似文献
1000.
Sei-Young Lim Kosuke Yamaguchi Masanori Itakura Miho Chikazawa Tomonari Matsuda Koji Uchida 《The Journal of biological chemistry》2022,298(2)
Lysine N-pyrrolation, a posttranslational modification, which converts lysine residues to Nε-pyrrole-L-lysine, imparts electronegative properties to proteins, causing them to mimic DNA. Apolipoprotein E (apoE) has been identified as a soluble receptor for pyrrolated proteins (pyrP), and accelerated lysine N-pyrrolation has been observed in apoE-deficient (apoE−/−) hyperlipidemic mice. However, the impact of pyrP accumulation consequent to apoE deficiency on the innate immune response remains unclear. Here, we investigated B-1a cells known to produce germline-encoded immunoglobulin M (IgM) from mice deficient in apoE and identified a particular cell population that specifically produces IgM antibodies against pyrP and DNA. We demonstrated an expansion of B-1a cells involved in IgM production in the peritoneal cavity of apoE−/− mice compared with wild-type mice, consistent with a progressive increase of IgM response in the mouse sera. We found that pyrP exhibited preferential binding to B-1a cells and facilitated the production of IgM. B cell receptor analysis of pyrP-specific B-1a cells showed restricted usage of gene segments selected from the germline gene set; most sequences contained high levels of non-templated-nucleotide additions (N-additions) that could contribute to junctional diversity of B cell receptors. Finally, we report that a subset of monoclonal IgM antibodies against pyrP/DNA established from the apoE−/− mice also contained abundant N-additions. These results suggest that the accumulation of pyrP due to apoE deficiency may influence clonal diversity in the pyrP-specific B cell repertoire. The discovery of these unique B-1a cells for pyrP/DNA provides a key link connecting covalent protein modification, lipoprotein metabolism, and innate immunity. 相似文献