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排序方式: 共有294条查询结果,搜索用时 15 毫秒
1.
Nirmal Mazumder Rodney K. Lyn Ragunath Singaravelu Andrew Ridsdale Douglas J. Moffatt Chih-Wei Hu Han-Ruei Tsai John McLauchlan Albert Stolow Fu-Jen Kao John Paul Pezacki 《PloS one》2013,8(6)
Hepatitis C virus (HCV) co-opts hepatic lipid pathways to facilitate its pathogenesis. The virus alters cellular lipid biosynthesis and trafficking, and causes an accumulation of lipid droplets (LDs) that gives rise to hepatic steatosis. Little is known about how these changes are controlled at the molecular level, and how they are related to the underlying metabolic states of the infected cell. The HCV core protein has previously been shown to independently induce alterations in hepatic lipid homeostasis. Herein, we demonstrate, using coherent anti-Stokes Raman scattering (CARS) microscopy, that expression of domain 2 of the HCV core protein (D2) fused to GFP is sufficient to induce an accumulation of larger lipid droplets (LDs) in the perinuclear region. Additionally, we performed fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotides [NAD(P)H], a key coenzyme in cellular metabolic processes, to monitor changes in the cofactor’s abundance and conformational state in D2-GFP transfected cells. When expressed in Huh-7 human hepatoma cells, we observed that the D2-GFP induced accumulation of LDs correlated with an increase in total NAD(P)H fluorescence and an increase in the ratio of free to bound NAD(P)H. This is consistent with an approximate 10 fold increase in cellular NAD(P)H levels. Furthermore, the lifetimes of bound and free NAD(P)H were both significantly reduced – indicating viral protein-induced alterations in the cofactors’ binding and microenvironment. Interestingly, the D2-expressing cells showed a more diffuse localization of NAD(P)H fluorescence signal, consistent with an accumulation of the co-factor outside the mitochondria. These observations suggest that HCV causes a shift of metabolic control away from the use of the coenzyme in mitochondrial electron transport and towards glycolysis, lipid biosynthesis, and building of new biomass. Overall, our findings demonstrate that HCV induced alterations in hepatic metabolism is tightly linked to alterations in NAD(P)H functional states. 相似文献
2.
Isolated testes of the locust Schistocerca gregaria were immersed in solutions of tritiated thymidine, cytidine, uridine, or arginine for short periods to study nucleic acid and protein synthesis during spermatogenesis. DNA synthesis in this tissue is completed prior to initiation of meiosis. Protein synthesis continues throughout the whole meiotic cycle as well as during spermatid development. Meiotic cells, except those in metaphase through early telophase, and early spermatids are also actively synthesizing RNA. The heteropycnotic X-chromosome does not produce RNA at any stage of spermatogenesis. The rates of protein and particularly RNA synthesis decrease as chromosome condensation progresses. Depression of RNA synthesis, however, is not always accompanied by cytologically detectable condensation of chromatin, since very little or no RNA is synthesized in spermatids in which chromatin condensation has barely begun. 相似文献
3.
Umesh C. Haldar Sanat K. Saha Ronald C. Beavis Nirmal K. Sinha 《Journal of Protein Chemistry》1996,15(2):177-184
Two trypsin inhibitors, LA-1 and LA-2, have been isolated from ridged gourd (Luffa acutangula Linn.) seeds and purified to homogeneity by gel filtration followed by ion-exchange chromatography. The isoelectric point is atpH 4.55 for LA-1 and atpH 5.85 for LA-2. The Stokes radius of each inhibitor is 11.4 å. The fluorescence emission spectrum of each inhibitor is similar to that of the free tyrosine. The biomolecular rate constant of acrylamide quenching is 1.0×109 M–1 sec–1 for LA-1 and 0.8 × 109 M–1 sec–1 for LA-2 and that of K2HPO4 quenching is 1.6×1011 M–1 sec–1 for LA-1 and 1.2×1011M–1 sec–1 for LA-2. Analysis of the circular dichroic spectra yields 40%-helix and 60%-turn for La-1 and 45%-helix and 55%-turn for LA-2. Inhibitors LA-1 and LA-2 consist of 28 and 29 amino acid residues, respectively. They lack threonine, alanine, valine, and tryptophan. Both inhibitors strongly inhibit trypsin by forming enzymeinhibitor complexes at a molar ratio of unity. A chemical modification study suggests the involvement of arginine of LA-1 and lysine of LA-2 in their reactive sites. The inhibitors are very similar in their amino acid sequences, and show sequence homology with other squash family inhibitors. 相似文献
4.
Trypsin-subtilisin inhibitor from marine turtle eggwhite refolded quantitatively from its fully reduced state atpH 8.5 in the presence of reduced and oxidized glutathione. The refolding process was studied by following the accompanying changes in inhibitory activity, fluorescence, sulfhydryl group titer, and hydrodynamic volume. The refolding process followed second-order kinetics with rate constants of 4.80×102 M–1 sec–1 for trypsin-inhibiting domain and 0.77× 102 M–1 sec–1 for subtilisin-inhibiting domain of the inhibitor at 30°C and their respective activation energies of the refolding process were 15.9 and 21.6 kcal/mol. Fluorescence intensity of the reduced inhibitor decreased with time of refolding until it corresponded to the intensity of the native inhibitor. The inhibitor contained 1–2%-helix, 40–42%-sheet, and 57–58% random coil structure. Refolded inhibitor gave a circular dichroic spectrum identical to that of the native inhibitor. A number of principal intermediates were detected as a function of the refolding time. Size-exclusion chromatography separated the intermediates differing in hydrodynamic volume (Stokes radius). The Stokes radius ranged from 23 Å (fully reduced inhibitor) to 18.8 Å (native inhibitor). Results indicated the independent refolding of two domains of the inhibitor and multiple pathways of folding were followed rather than an ordered sequential pathway. 相似文献
5.
Bahman Tabaraie Bal Krishan Sharma Praveen Rishi nee Sharma Rakesh Sehgal Nirmal Kumar Ganguly 《Microbiology and immunology》1994,38(7):553-559
Porins were prepared from smooth strain of Salmonella typhi 0–901 and chemotype of rough mutant of S. typhimurium Ra-30. Mice were immunized with both the porin preparations in different groups and challenged with S. typhimurium LT2–71 and S. enteritidis SH-1269. Porin immunized mice showed significant protection (P <0.01) against challenge with homologous as well as heterologous strains. Hence, the use of porins may be attempted in future to protect against salmonellosis. 相似文献
6.
Summary DNA synthesis and mitosis were initiated in cultured tobacco pith tissue by means of IAA and kinetin. DNA classes were determined by microspectrophotometric measurements (Feulgen); autoradiographs (tritiated thymidine) served to ascertain whether or not nuclei had undergone DNA synthesis during culture.All mitoses in new cells (resulting from divisions in culture) were diploid and had been preceded by DNA synthesis in culture.Whereas many of the old cells (which had not previously divided in culture) found in diploid or polyploid mitosis had undergone DNA synthesis during culture, others had not. Such non-radioactive mitoses still occurred after 16 days.In view of this, a 4 C nucleus in differentiated tissue should be considered as potentially both diploid and tetraploid, for it appears impossible to predict whether it would, upon restoration of conditions conducive to DNA synthesis and mitosis, enter a diploid mitosis or, after undergoing DNA synthesis, a tetraploid one.A high nuclear DNA content seems to have a much more inhibiting effect on the onset of DNA doubling than on that of mitosis.Somatic polyploidization is understood as the result of two DNA doublings between which mitosis was omitted, or aborted, or in effect undone by a failure of cytokinesis leading to fusion during a later mitosis.This work has been supported by research grants to K. Patau from the U.S. Public Health Service (grant No. C-3313) and the American Cancer Society. 相似文献
7.
Umesh C. Haldar Sanat K. Saha Ronald C. Beavis Nirmal K. Sinha 《The protein journal》1996,15(2):177-184
Two trypsin inhibitors, LA-1 and LA-2, have been isolated from ridged gourd (Luffa acutangula Linn.) seeds and purified to homogeneity by gel filtration followed by ion-exchange chromatography. The isoelectric point is atpH 4.55 for LA-1 and atpH 5.85 for LA-2. The Stokes radius of each inhibitor is 11.4 å. The fluorescence emission spectrum of each inhibitor is similar to that of the free tyrosine. The biomolecular rate constant of acrylamide quenching is 1.0×109 M?1 sec?1 for LA-1 and 0.8 × 109 M?1 sec?1 for LA-2 and that of K2HPO4 quenching is 1.6×1011 M?1 sec?1 for LA-1 and 1.2×1011M?1 sec?1 for LA-2. Analysis of the circular dichroic spectra yields 40%α-helix and 60%Β-turn for La-1 and 45%α-helix and 55%Β-turn for LA-2. Inhibitors LA-1 and LA-2 consist of 28 and 29 amino acid residues, respectively. They lack threonine, alanine, valine, and tryptophan. Both inhibitors strongly inhibit trypsin by forming enzymeinhibitor complexes at a molar ratio of unity. A chemical modification study suggests the involvement of arginine of LA-1 and lysine of LA-2 in their reactive sites. The inhibitors are very similar in their amino acid sequences, and show sequence homology with other squash family inhibitors. 相似文献
8.
Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction 总被引:3,自引:0,他引:3
Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12)in which LPA was ligated acutely. In the left lung,O2 uptake after acute ligation was16 ± 3 ml/min and was similar to the chronic model, whereasCO2 output in the control group was 27 ± 3 ml/min compared with 79 ± 12 ml/min in the chronic preparation (P < 0.05).We conclude that LPA ligation causes marked angiogenesis in BCS that iscapable of performing some gas-exchange functions. 相似文献
9.
Charan Nirmal B.; Johnson Shane R.; Lakshminarayan S.; Thompson William H.; Carvalho Paula 《Journal of applied physiology》1997,82(2):686-692
Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan,William H. Thompson, and Paula Carvalho. Nitric oxide and-adrenergic agonist-induced bronchial arterial vasodilation.J. Appl. Physiol. 82(2): 686-692, 1997.In anesthetized sheep, we measured bronchial blood flow(br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) givenfor 5 min and 5 ml of aerosolized isoetharine (1.49 × 102 M concentration).NO and isoetharine increased br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min,respectively (n = 5).Administration of NO immediately after isoetharine further increasedbr to 57.3 ± 15.1 ml/min. NO synthase inhibitorN-nitro-L-arginine methyl esterhydrochloride (L-NAME; 30 mg/kg, in 20 ml salinegiven iv) decreased br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiatevasodilator effects of each other. In three other sheep, afterL-NAME, three sequential doses of isoetharine increased br from 10.2 ± 3.4 to11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min,respectively, indicating that effects of isoetharine are predominantlymediated through synthesis of NO. When this was followed by threesequential administrations of NO, br increased by146, 172, and 185%, respectively. Thus in the bronchial circulationthere seems to be a close interaction between adenosine3,5-cyclic monophosphate- and guanosine3,5-cyclic monophosphate-mediated vasodilatation. 相似文献
10.
N. Krishnakumar N. K. Sulfikkarali S. Manoharan R. Madhavan Nirmal 《Molecular and cellular biochemistry》2013,382(1-2):27-36
The aim of the present study is to investigate the chemopreventive effects of the prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) in modifying the functional, structural, and compositional changes at the molecular level during 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that a significant increase in the amount of proteins and nucleic acid contents and a decrease in the amount of lipids and glycogen contents are observed in DMBA-induced tumor tissues. In addition, in tumor tissues a decrease in lipid order and a significant increase in membrane dynamics were noticed. Further, the composition and secondary structure of proteins were found to be altered, which indicates some important structural alterations in the existing proteins and/or the expression of new types of proteins occurring under the tumor transformation. Furthermore, oral administration of free NAR and NARNPs significantly increased lipids and their order as well as increased the glycogen contents and decreased the levels of proteins and nucleic acid contents. On a comparative basis, NARNPs were found to have a more potent antitumor effect than free NAR in completely preventing the formation of squamous cell carcinoma and in improving the biochemical constituents to a normal range in DMBA-induced HBP carcinogenesis. The present study further shows a great potential of FT-IR spectroscopy as a complimentary tool for the screening of various anticancer drugs and follow-up, which may allow faster response to critical problems arising during treatment. 相似文献