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971.
In continuous cultures of Chlorella fusca under steady state conditions, the CO2-fixation rate, the ATP-level, the apparent rate of photophosphorylation as calculated from the changes in the ATP-level during light to dark or dark to light transients and the energy charge were measured at various environmental conditions. During growth the energy charge was around 0.64. CO2-assimilation and the apparent ATP-synthesis were strongly dependant on light intensity, however the ATP-level was independant on it. Since the rates of apparent ATP-synthesis and of the CO2-fixation do not seem to be strictly correlated in a logic way when environmental factors are changed and furthermore the stoichiometry of 3 ATP necessary per CO2 fixed was never achieved, the described method frequently used for procaryotes to determine the in vivo rate of phosphorylation does not give valid results in highly compartimented eukaryotic cells. 相似文献
972.
C. Panter-Brick 《European journal of applied physiology and occupational physiology》1992,64(5):477-484
Three hundred and six measurements of energy expenditure by indirect calorimetry of sitting at rest and self-paced activity were made on 41 men, 48 women and 6 adolescents in a mountain village of Nepal. Except for walking and carrying uphill, measured activities fell within the range of values for light to moderate effort, despite appearing physically demanding. Villagers tended to reduce travel speed when carrying heavy loads (54-102% of body mass on various inclines), averaging a moderate level of energy expenditure which could be sustained throughout the day. Such moderately demanding work was also assumed by pregnant, lactating women and young adolescents. Pregnant women worked more slowly at some tasks, but did not differentiate themselves from their non-pregnant, non-lactating counterparts for travel on the mountain side. 相似文献
973.
Abstract: Impaired energy metabolism may contribute to the pathogenesis of late-onset neurodegenerative disorders such as Alzheimer's disease by increasing neuronal vulnerability to excitotoxic damage through the NMDA receptor. The effects of metabolic impairment on the striatum have been extensively examined, but relatively little is known regarding the vulnerability of the hippocampus. To examine the effect of metabolic impairment on the hippocampal formation, malonate (0.25–2.5 µmol), a reversible inhibitor of succinate dehydrogenase, was administered by stereotaxic injection into the hippocampus of male Sprague-Dawley rats. Neuronal loss was assessed by Nissl stain, and immunocytochemistry was used to examine cytoskeletal disruption. Malonate produced a dose-dependent lesion in which CA1 pyramidal neurons were most vulnerable, followed by CA3 and dentate gyrus. Cytoskeletal alterations included the loss of microtubule-associated protein 2 (MAP2) and dendritic MAP1B immunoreactivity, whereas axonal MAP1B and τ proteins were relatively spared. Spatially and temporally correlated with the loss of MAP2 was an increase in the immunoreactivity of calpain-cleaved spectrin. A similar pattern of neuronal damage and cytoskeletal disruption was produced by intrahippocampal injection of quinolinate (0.1 µmol), an NMDA agonist. Although these results are consistent with the hypothesis that metabolic impairment results in excitotoxic death, MK-801 (dizocilpine maleate), a noncompetitive NMDA receptor antagonist, did not attenuate the lesions produced by malonate but was effective against quinolinate. The results suggest that NMDA receptor activation is not required for malonate-induced damage in the hippocampal formation. 相似文献
974.
Aims
This experiment investigated the effects of sub-chronic aluminum chloride (AlCl3) exposure on rat ovaries.Main methods
Eighty female Wistar (5 weeks old) rats, weighed 110–120 g, were randomly divided into four treatment groups: control group (CG), low-dose group (LG, 64 mg/kg BW AlCl3), mid-dose group (MG, 128 mg/kg BW AlCl3) and high-dose group (HG, 256 mg/kg BW AlCl3). The AlCl3 was administered in drinking water for 120 days. The ovarian ultrastructure was observed. The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), succinate dehydrogenase (SDH), Na+–K+-ATPase, Mg2 +-ATPase and Ca2 +-ATPase, the contents of Fe, Cu and Zn, and the protein expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in the ovary were determined.Key findings
The results showed that the structure of the ovary was disrupted, the activities of ALP, ACP, SDH, Na+–K+-ATPase, Mg2 +-ATPase and Ca2 +-ATPase, the contents of Zn, Fe and the protein expression of FSHR and LHR were lowered, and the content of Cu was increased in AlCl3-treated rats than those in control.Significance
The results indicate that sub-chronic AlCl3 exposure caused the damage of the ovarian structure, the disturbed metabolism of Fe, Zn and Cu and the decreased activities of Na+–K+-ATPase, Mg2 +-ATPase and Ca2 +-ATPase in the ovary, which could result in suppressed energy supply in the ovary. A combination of suppression of energy supply and reduction of expression of FSHR and LHR could inhibit ovulation and corpus luteum development, leading to infertility in female rats. 相似文献975.
Magnus C. Mayer Daniela Kaden Linda Schauenburg Mark A. Hancock Philipp Voigt Dirk Roeser Christian Barucker Manuel E. Than Michael Schaefer Gerhard Multhaup 《The Journal of biological chemistry》2014,289(27):19019-19030
The amyloid precursor protein (APP) and the APP-like proteins 1 and 2 (APLP1 and APLP2) are a family of multidomain transmembrane proteins possessing homo- and heterotypic contact sites in their ectodomains. We previously reported that divalent metal ions dictate the conformation of the extracellular APP E2 domain (Dahms, S. O., Könnig, I., Roeser, D., Gührs, K.-H., Mayer, M. C., Kaden, D., Multhaup, G., and Than, M. E. (2012) J. Mol. Biol. 416, 438–452), but unresolved is the nature and functional importance of metal ion binding to APLP1 and APLP2. We found here that zinc ions bound to APP and APLP1 E2 domains and mediated their oligomerization, whereas the APLP2 E2 domain interacted more weakly with zinc possessing a less surface-exposed zinc-binding site, and stayed monomeric. Copper ions bound to E2 domains of all three proteins. Fluorescence resonance energy transfer (FRET) analyses examined the effect of metal ion binding to APP and APLPs in the cellular context in real time. Zinc ions specifically induced APP and APLP1 oligomerization and forced APLP1 into multimeric clusters at the plasma membrane consistent with zinc concentrations in the blood and brain. The observed effects were mediated by a novel zinc-binding site within the APLP1 E2 domain as APLP1 deletion mutants revealed. Based upon its cellular localization and its dominant response to zinc ions, APLP1 is mainly affected by extracellular zinc among the APP family proteins. We conclude that zinc binding and APP/APLP oligomerization are intimately linked, and we propose that this represents a novel mechanism for regulating APP/APLP protein function at the molecular level. 相似文献
976.
Takashi Tanaka Kazuaki Nagashima Nobuya Inagaki Hidetaka Kioka Seiji Takashima Hajime Fukuoka Hiroyuki Noji Akira Kakizuka Hiromi Imamura 《The Journal of biological chemistry》2014,289(4):2205-2216
In pancreatic islets, insulin secretion occurs via synchronous elevation of Ca2+ levels throughout the islets during high glucose conditions. This Ca2+ elevation has two phases: a quick increase, observed after the glucose stimulus, followed by prolonged oscillations. In these processes, the elevation of intracellular ATP levels generated from glucose is assumed to inhibit ATP-sensitive K+ channels, leading to the depolarization of membranes, which in turn induces Ca2+ elevation in the islets. However, little is known about the dynamics of intracellular ATP levels and their correlation with Ca2+ levels in the islets in response to changing glucose levels. In this study, a genetically encoded fluorescent biosensor for ATP and a fluorescent Ca2+ dye were employed to simultaneously monitor the dynamics of intracellular ATP and Ca2+ levels, respectively, inside single isolated islets. We observed rapid increases in cytosolic and mitochondrial ATP levels after stimulation with glucose, as well as with methyl pyruvate or leucine/glutamine. High ATP levels were sustained as long as high glucose levels persisted. Inhibition of ATP production suppressed the initial Ca2+ increase, suggesting that enhanced energy metabolism triggers the initial phase of Ca2+ influx. On the other hand, cytosolic ATP levels did not fluctuate significantly with the Ca2+ level in the subsequent oscillation phases. Importantly, Ca2+ oscillations stopped immediately before ATP levels decreased significantly. These results might explain how food or glucose intake evokes insulin secretion and how the resulting decrease in plasma glucose levels leads to cessation of secretion. 相似文献
977.
Robyn Flynn Kevin Chapman Mircea Iftinca Reem Aboushousha Diego Varela Christophe Altier 《The Journal of biological chemistry》2014,289(24):16675-16687
The transient receptor potential channel vanilloid type 1 (TRPV1) is a non-selective cation channel expressed in sensory neurons of the dorsal root and trigeminal ganglia. TRPV1 is a polymodal channel activated by noxious heat, capsaicin, and protons. As a sensor for noxious stimuli, TRPV1 channel has been described as a key contributor to pain signaling. To form a functional channel, TRPV1 subunits must assemble into tetramers, and several studies have identified the TRPV1 C terminus as an essential element in subunit association. Here we combined biochemical assays with electrophysiology and imaging-based bimolecular fluorescence complementation (BiFC) and bioluminescence resonance energy transfer (BRET) in live cells to identify a short motif in the C-terminal tail of the TRPV1 subunit that governs channel assembly. Removing this region through early truncation or targeted deletion results in loss of subunit association and channel function. Importantly, we found that interfering with TRPV1 subunit association using a plasma membrane-tethered peptide attenuated mechanical and thermal hypersensitivity in two mouse models of inflammatory hyperalgesia. This represents a novel mechanism to disrupt TRPV1 subunit assembly and hence may offer a new analgesic tool for pain relief. 相似文献
978.
Expression of Adipocyte Biomarkers in a Primary Cell Culture Models Reflects Preweaning Adipobiology
Dinh-Toi Chu Elzbieta Malinowska Barbara Gawronska-Kozak Leslie P. Kozak 《The Journal of biological chemistry》2014,289(26):18478-18488
A cohort of genes was selected to characterize the adipogenic phenotype in primary cell cultures from three tissue sources. We compared the quantitative expression of biomarkers in culture relative to their expression in vivo because the mere presence or absence of expression is minimally informative. Although all biomarkers analyzed have biochemical functions in adipocytes, the expression of some of the biomarkers varied enormously in culture relative to their expression in the adult fat tissues in vivo, i.e. inguinal fat for white adipocytes and brite cells, interscapular brown adipose tissue for brown adipocytes, and ear mesenchymal stem cells for white adipocytes from adult mice. We propose that the pattern of expression in vitro does not reflect gene expression in the adult mouse; rather it is predominantly the expression pattern of adipose tissue of the developing mouse between birth and weaning. The variation in gene expression among fat depots in both human and rodent has been an extensively studied phenomenon, and as recently reviewed, it is related to subphenotypes associated with immune function, the inflammatory response, fat depot blood flow, and insulin sensitivity. We suggest that adipose tissue biology in the period from birth to weaning is not just a staging platform for the emergence of adult white fat but that it has properties to serve the unique needs of energy metabolism in the newborn. A case in point is the differentiation of brite cells that occurs during this period followed by their involution immediately following weaning. 相似文献
979.
David W. Nelson Yu Gao Mei-I Yen Chi-Liang Eric Yen 《The Journal of biological chemistry》2014,289(25):17338-17349
The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. 相似文献
980.
Alexandre Beautrait Kevin R. Michalski Thomas S. Lopez Katelynn M. Mannix Devin J. McDonald Amber R. Cutter Christopher B. Medina Aaron M. Hebert Charnelle J. Francis Michel Bouvier John J. G. Tesmer Rachel Sterne-Marr 《The Journal of biological chemistry》2014,289(36):25262-25275
G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiating the processes of desensitization and β-arrestin-dependent signaling. Interaction of GRKs with activated receptors serves to stimulate their kinase activity. The extreme N-terminal helix (αN), the kinase small lobe, and the active site tether (AST) of the AGC kinase domain have previously been implicated in mediating the allosteric activation. Expanded mutagenesis of the αN and AST allowed us to further assess the role of these two regions in kinase activation and receptor phosphorylation in vitro and in intact cells. We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated α2A-adrenergic receptors (α2AARs) in living cells. The bioluminescence resonance energy transfer signal exhibited a biphasic response to norepinephrine concentration, suggesting that GRK2 is recruited to Gβγ and α2AAR with EC50 values of 15 nm and 8 μm, respectively. We show that mutations in αN (L4A, V7E, L8E, V11A, S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or potentiate receptor phosphorylation and/or recruitment. We suggest that a surface of GRK2, including Leu4, Val7, Leu8, Val11, and Ser12, directly interacts with receptors, whereas residues such as Asp10, Tyr13, Ala16, Met17, Gly475, Val477, and Ile485 are more important for kinase domain closure and activation. Taken together with data on GRK1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G protein-coupled receptors, but there may be unique interactions that influence selectivity. 相似文献