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Honaker RW Dhiman RK Narayanasamy P Crick DC Voskuil MI 《Journal of bacteriology》2010,192(24):6447-6455
The DosR regulon in Mycobacterium tuberculosis is involved in respiration-limiting conditions, its induction is controlled by two histidine kinases, DosS and DosT, and recent experimental evidence indicates DosS senses either molecular oxygen or a redox change. Under aerobic conditions, induction of the DosR regulon by DosS, but not DosT, was observed after the addition of ascorbate, a powerful cytochrome c reductant, demonstrating that DosS responds to a redox signal even in the presence of high oxygen tension. During hypoxic conditions, regulon induction was attenuated by treatment with compounds that occluded electron flow into the menaquinone pool or decreased the size of the menaquinone pool itself. Increased regulon expression during hypoxia was observed when exogenous menaquinone was added, demonstrating that the menaquinone pool is a limiting factor in regulon induction. Taken together, these data demonstrate that a reduced menaquinone pool directly or indirectly triggers induction of the DosR regulon via DosS. Biochemical analysis of menaquinones upon entry into hypoxic/anaerobic conditions demonstrated the disappearance of the unsaturated species and low-level maintenance of the mono-saturated menaquinone. Relative to the unsaturated form, an analog of the saturated form is better able to induce signaling via DosS and rescue inhibition of menaquinone synthesis and is less toxic. The menaquinone pool is central to the electron transport system (ETS) and therefore provides a mechanistic link between the respiratory state of the bacilli and DosS signaling. Although this report demonstrates that DosS responds to a reduced ETS, it does not rule out a role for oxygen in silencing signaling. 相似文献
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Usha Singh Ajit Kumar Rajesh Sinha Sushma Manral Shvetambri Arora Sant Ram Rakesh K. Mishra Prachi Gupta Surendra K. Bansal Ashok K. Prasad Shyam Biswal Virinder S. Parmar Hanumantharao G. Raj 《Chemico-biological interactions》2010,185(3):263-270
Polyphenols, coumarin (1,2-benzopyrone) and chromone (1,4-benzopyrone), are naturally occurring constituent of variety of plant species. They have attracted immense interest because of their diverse pharmacological activities. Not much was known about biological activities of acetyl derivative (polyphenolic acetates) of parent polyphenols. In previous investigations, we have conclusively established calreticulin transacetylase catalyzed activation of endothelial nitric oxide synthase (eNOS) by polyphenolic acetates. In the present work, calreticulin transacetylase of human peripheral blood mononuclear cells was characterized with respect to specificity for various polyphenolic acetates and its role in the activation of TNF-α induced nitric oxide synthase (iNOS). Peripheral blood mononuclear cells incubated with a model polyphenolic acetate, 7,8-diacetoxy-4-methylcoumarin (DAMC), along with l-arginine caused activation of NOS. The incubation of peripheral blood mononuclear cells with TNF-α and DAMC resulted in increased production of NO as compared to TNF-α alone. This increased NO production was attenuated by l-Nω-nitro-l-arginine methyl ester (l-NAME), a well known non-specific inhibitor of NOS, and 1400W (N-[3-(aminomethyl) benzyl] acetamidine), a specific inhibitor of human iNOS. These results substantiate the CRTAase catalyzed activation of iNOS. Further, expression of NOS isoforms by semi-quantitative PCR and real-time RT-PCR confirms the preponderance of iNOS in TNF-α treated peripheral blood mononuclear cells over the untreated one. It was also observed that polyphenolic acetates inhibit TNF-α mediated release of IL-6 from peripheral blood mononuclear cells. 相似文献
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Gladwin MT Raat NJ Shiva S Dezfulian C Hogg N Kim-Shapiro DB Patel RP 《American journal of physiology. Heart and circulatory physiology》2006,291(5):H2026-H2035
Accumulating evidence suggests that the simple and ubiquitous anion salt, nitrite (NO(2)(-)), is a physiological signaling molecule with potential roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Human and animal studies of nitrite treatment and NO gas inhalation provide evidence that nitrite mediates many of the systemic therapeutic effects of NO gas inhalation, including peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue infarction. With regard to nitrite-dependent hypoxic signaling, biochemical and physiological studies suggest that hemoglobin possesses an allosterically regulated nitrite reductase activity that reduces nitrite to NO along the physiological oxygen gradient, potentially contributing to hypoxic vasodilation. An expanded consideration of nitrite as a hypoxia-dependent intrinsic signaling molecule has opened up a new field of research and therapeutic opportunities for diseases associated with regional hypoxia and vasoconstriction. 相似文献
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Bacterial community structure of a pesticide-contaminated site and assessment of changes induced in community structure during bioremediation 总被引:1,自引:0,他引:1
The introduction of culture-independent molecular screening techniques, especially based on 16S rRNA gene sequences, has allowed microbiologists to examine a facet of microbial diversity not necessarily reflected by the results of culturing studies. The bacterial community structure was studied for a pesticide-contaminated site that was subsequently remediated using an efficient degradative strain Arthrobacter protophormiae RKJ100. The efficiency of the bioremediation process was assessed by monitoring the depletion of the pollutant, and the effect of addition of an exogenous strain on the existing soil community structure was determined using molecular techniques. The 16S rRNA gene pool amplified from the soil metagenome was cloned and restriction fragment length polymorphism studies revealed 46 different phylotypes on the basis of similar banding patterns. Sequencing of representative clones of each phylotype showed that the community structure of the pesticide-contaminated soil was mainly constituted by Proteobacteria and Actinomycetes. Terminal restriction fragment length polymorphism analysis showed only nonsignificant changes in community structure during the process of bioremediation. Immobilized cells of strain RKJ100 enhanced pollutant degradation but seemed to have no detectable effects on the existing bacterial community structure. 相似文献
118.
Bone is a composite biomaterial, which is formed, when proteins constituting collagen fibers attract calcium, phosphate and hydroxide ions in solution to nucleate atop the fibers. It grows into a hard structure of tiny crystallites of hydroxyapatite, aligned along the long axis of collagen fibers. The present work reports the stimulating effect of static magnetic field on microstructure and mineralization process of bone repair. A unilateral transverse fracture of mid-shaft of metacarpal was surgically created in healthy goats under thiopental sedation and xylocaine analgesia. Two bar magnets (approximately 800 gauss/cm2 field strength) were placed across the fracture line at opposite pole alignment immobilized in Plaster of Paris (POP) splint bandage for static magnetic field stimulation. Radiographs were taken at weekly intervals up to 45 days. Results show that formation of extra-cellular matrix and its microstructure can be influenced by non-invasive physical stimulus (magnetic field) for achieving an enhanced osteogenesis, leading to quicker regeneration of bone tissue in goats. X-ray diffraction (XRD) patterns of treated (magnetic field-exposed) and control samples revealed the presence and orientation of crystalline structures. Intensity of diffraction peaks corresponding to 310 and 222 planes were enhanced with respect to 211 families of reflections, indicating preferential alignment of the crystals. Also, the percent crystallinity and crystal size were increased in treated samples. The study provides a biophysical basis for augmented fracture healing under the influence of semi-aligned static magnetic field applied across the fracture line. 相似文献
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Daily oral administration of isoproterenol hydrochloride (60 mg/kg body weight; for 30 days) a beta-receptor agonist to normal innervated and denervated adult male Swiss albino mice confirmed its ability to induce skeletal muscle hypertrophy and reverse denervation atrophy respectively. Measurement of total tissue proteins and dry muscle mass showed 15-17% increase with 6% rise of hypertrophy index in gastrocnemius muscle. Hydroxyproline assay employed to measure the total tissue collagen exhibited 45% increase in collagen in normal innervated gastrocnemius muscle in response to beta agonist treatment. beta-adrenoceptor agonist ameliorated denervation atrophy along with further increase in collagen content of denervated gastrocnemius muscle. 相似文献