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81.
Li Y Dash RK Kim J Saidel GM Cabrera ME 《American journal of physiology. Cell physiology》2009,296(1):C25-C46
Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an approximately 70% decrease (or approximately 3-fold increase) in cytosolic redox state and an approximately 35% decrease (or approximately 25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an approximately 50% increase (or approximately 35% decrease) in cytosolic redox state and an approximately 30% increase (or approximately 25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the model simulations of exercise response are consistent with the hypothesis that mitochondrial NADH/NAD+ shuttling activity and muscle glycogen stores affect primarily the cytosolic redox state. Furthermore, muscle lactate production is regulated primarily by the cytosolic redox state. 相似文献
82.
K. P. Krishnan Rupesh Kumar Sinha Kiran Krishna Shanta Nair S. M. Singh 《Polar Biology》2009,32(12):1765-1778
The significance of freshwater systems in global manganese cycles is well appreciated. Yet, the polar systems, which encompass
the largest freshwater repository in the world, have been least studied for their role in manganese cycling. Here, we present
results from a study that was conducted in the brackish water lakes in the Larsemann Hills region (east Antarctica). The rate
of in situ manganese oxidation ranged from 0.04 to 3.96 ppb day−1. These lakes harbor numerous manganese-oxidizing bacteria (105 to 106 CFU l−1), predominantly belonging to genera Shewanella, Pseudomonas and an unclassified genus in the family Oxalobacteriaceae. Experiments were conducted with representatives of predominant
genera to understand their contribution to Mn cycling and also to assess their metabolic capabilities in the presence of this
metal. In general, the total and respiring cell counts were stimulated to a maximum when the growth medium was amended with
10 mM manganese. The addition of manganese promoted the use of d-mannitol, maltose, etc., but inhibited the use of maltotriose, l-serine and glycyl l-glutamic acid. The bacterial isolates were able to catalyze both the redox reactions in manganese cycling. In vitro manganese
oxidation rates ranged from 3 to 147 ppb day−1, while manganese reduction rates ranged from 35 to 213 ppb day−1. It was also observed that the maximum stimulation of manganese oxidation occurred in the presence of cobalt (81 ± 57 ppb day−1), rather than iron (37 ± 16 ppb day−1) and nickel (40 ± 47 ppb day−1). Our studies suggest that cobalt could have a more profound role in manganese oxidation, while nickel promoted manganese
reduction in polar aquatic systems. 相似文献
83.
84.
Background
Biological networks characterize the interactions of biomolecules at a systems-level. One important property of biological networks is the modular structure, in which nodes are densely connected with each other, but between which there are only sparse connections. In this report, we attempted to find the relationship between the network topology and formation of modular structure by comparing gene co-expression networks with random networks. The organization of gene functional modules was also investigated. 相似文献85.
Circumvention of drug resistance still remains a challenge in the development of anticancer therapeutics. Combinational nano-formulations provide many avenues for effective cancer therapy and reversal of drug resistance. In the current study, combination of biochanin A (BioA) and doxorubicin (DOX) in liposomes were prepared and studied for its potential to reverse DOX resistance in COLO205 cells. After development and validation of DOX resistant cells of COLO205 (ColoR), dosing ratio of DOX and BioA for reversal of DOX resistance was determined by co-treatment in ColoR cells. As limited solubility and analytical data available for BioA, therefore solubility was studied for BioA and analytical method was developed for the combination. Combinational liposomes were prepared and optimized for both lipid content and surface charge by evaluating size, polydispersity index, zeta potential, and encapsulation efficiency. The optimized formulation had a size about 125 nm; zeta potential of ?19.5 mV and 70% encapsulation efficiency (EE) for BioA. Thus, prepared combinational liposomes of DOX and BioA were evaluated for its cellular uptake and efficacy to reverse DOX resistance. From the study, increased DOX uptake and promising effect for reversal of DOX resistance was observed. 相似文献
86.
87.
Ca2+ is an important regulatory ion and alteration of mitochondrial Ca2+ homeostasis can lead to cellular dysfunction and apoptosis. Ca2+ is transported into respiring mitochondria via the Ca2+ uniporter, which is known to be inhibited by Mg2+. This uniporter-mediated mitochondrial Ca2+ transport is also shown to be influenced by inorganic phosphate (Pi). Despite a large number of experimental studies, the kinetic mechanisms associated with the Mg2+ inhibition and Pi regulation of the uniporter function are not well established. To gain a quantitative understanding of the effects of Mg2+ and Pi on the uniporter function, we developed here a mathematical model based on known kinetic properties of the uniporter and presumed Mg2+ inhibition and Pi regulation mechanisms. The model is extended from our previous model of the uniporter that is based on a multistate catalytic binding and interconversion mechanism and Eyring's free energy barrier theory for interconversion. The model satisfactorily describes a wide variety of experimental data sets on the kinetics of mitochondrial Ca2+ uptake. The model also appropriately depicts the inhibitory effect of Mg2+ on the uniporter function, in which Ca2+ uptake is hyperbolic in the absence of Mg2+ and sigmoid in the presence of Mg2+. The model suggests a mixed-type inhibition mechanism for Mg2+ inhibition of the uniporter function. This model is critical for building mechanistic models of mitochondrial bioenergetics and Ca2+ handling to understand the mechanisms by which Ca2+ mediates signaling pathways and modulates energy metabolism. 相似文献
88.
Chaturvedi U Kalim S Desai G Ratta B Kumar R Ravindra PV Kumar S Dash BB Tiwari S Sahoo AP Tiwari AK 《Indian journal of experimental biology》2011,49(2):140-145
Newcastle disease (ND) is highly contagious, economically important viral disease affecting most of avian species worldwide. Newcastle disease virus (NDV) has single stranded negative sense RNA genome which encodes for six structural and two non-structural proteins. Envelope glycoproteins i.e. hemagglutinin-neuraminidase (HN) and the fusion (F), elicit protective immune response. In this study, HN and F genes of velogenic (virulent) strain were amplified and cloned at multiple cloning sites A and B, respectively into pIRES bicistronic vector for use as bivalent DNA vaccine against ND. The recombinant plasmid was characterized for its orientation by restriction enzyme digestion and PCR. Expression of HN and F genes was assessed in transfected Vero cells at RNA level using RT-PCR in total RNA as well as protein level using IFAT, IPT and western blot using NDV specific antiserum. All these experiments confirmed that HN and F genes cloned in recombinant pIRES.nd.hn.f are functionally active. The recombinant construct is being evaluated as DNA vaccine against ND. 相似文献
89.
90.
Lewis ND Asim M Barry DP de Sablet T Singh K Piazuelo MB Gobert AP Chaturvedi R Wilson KT 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(6):3632-3641
Helicobacter pylori infection persists for the life of the host due to the failure of the immune response to eradicate the bacterium. Determining how H. pylori escapes the immune response in its gastric niche is clinically important. We have demonstrated in vitro that macrophage NO production can kill H. pylori, but induction of macrophage arginase II (Arg2) inhibits inducible NO synthase (iNOS) translation, causes apoptosis, and restricts bacterial killing. Using a chronic H. pylori infection model, we determined whether Arg2 impairs host defense in vivo. In C57BL/6 mice, expression of Arg2, but not arginase I, was abundant and localized to gastric macrophages. Arg2(-/-) mice had increased histologic gastritis and decreased bacterial colonization compared with wild-type (WT) mice. Increased gastritis scores correlated with decreased colonization in individual Arg2(-/-) mice but not in WT mice. When mice infected with H. pylori were compared, Arg2(-/-) mice had more gastric macrophages, more of these cells were iNOS(+), and these cells expressed higher levels of iNOS protein, as determined by flow cytometry and immunofluorescence microscopy. There was enhanced nitrotyrosine staining in infected Arg2(-/-) versus WT mice, indicating increased NO generation. Infected Arg2(-/-) mice exhibited decreased macrophage apoptosis, as well as enhanced IFN-γ, IL-17a, and IL-12p40 expression, and reduced IL-10 levels consistent with a more vigorous Th1/Th17 response. These studies demonstrate that Arg2 contributes to the immune evasion of H. pylori by limiting macrophage iNOS protein expression and NO production, mediating macrophage apoptosis, and restraining proinflammatory cytokine responses. 相似文献