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101.
This article recapitulates the scientific advancement towards the greener synthesis of silver nanoparticles. Applications of noble metals have increased throughout human civilization, and the uses for nano-sized particles are even more remarkable. “Green” nanoparticle synthesis has been achieved using environmentally acceptable solvent systems and eco-friendly reducing and capping agents. Numerous microorganisms and plant extracts have been applied to synthesize inorganic nanostructures either intracellularly or extracellularly. The use of nanoparticles derived from noble metals has spread to many areas including jewelery, medical fields, electronics, water treatment and sport utilities, thus improving the longevity and comfort in human life. The application of nanoparticles as delivery vehicles for bactericidal agents represents a new paradigm in the design of antibacterial therapeutics. Orientation, size and physical properties of nanoparticles influences the performance and reproducibility of a potential device, thus making the synthesis and assembly of shape- and size-controlled nanocrystals an essential component for any practical application. This need has motivated researchers to explore different synthesis protocols. 相似文献
102.
Ionizing radiation is an important genotoxic agent. Protecting against this form of toxicant, especially by a dietary component, has several potential applications. In the present study, we have examined the ability of vanillin (4-hydroxy-3-methoxybenzaldehyde), a naturally occurring food flavouring agent, to inhibit radiation-induced DNA damage measured as strand breaks under in vitro, ex vivo and in vivo conditions besides the possible mechanisms behind the observed protection. Our study showed that there was a concentration-dependent inhibition of the disappearance of super-coiled (ccc) form of plasmid pBR322 (in vitro) upon exposure to 50 Gy of gamma-radiation. Presence of 0.5 mM vanillin has a dose-modifying factor (DMF) of 6.75 for 50% inactivation of ccc form. Exposure of human peripheral blood leucocytes (ex vivo) to gamma-radiation causes strand breaks in the cellular DNA, as assessed by comet assay. When leucocytes were exposed to 2 Gy of gamma-radiation there was an increase in parameters of comet assay such as %DNA in tail, tail length, 'tail moment' and 'Olive tail moment'. The presence of 0.5 mM vanillin during irradiation significantly reduced these parameters. Damage to DNA in mouse peripheral blood leucocytes after whole-body exposure of mice (in vivo) to gamma-radiation was studied at 1 and 2 h post-irradiation. There was recovery of DNA damage in terms of the above-mentioned parameters at 2 h post-irradiation. This was more than that observed at 1 h. The recovery was more in vanillin treated mice. Hence our studies showed that vanillin offers protection to DNA against radiation-induced damage possibly imparting a role other than modulation of DNA repair. To examine the possible mechanisms of radioprotection, in terms of radiation-derived radicals, we carried out the reaction of vanillin with ABTS*(+) radical spectrophotometrically besides with DNA peroxyl and carbonyl radicals by using pulse radiolysis. Our present investigations show that vanillin has ability to protect against DNA damage in plasmid pBR322, human and mouse peripheral blood leucocytes and splenic lymphocytes besides enhancing survival in splenic lymphocytes against gamma-radiation, and that the possible mechanism may involve scavenging of radicals generated during radiation, apart from modulation of DNA repair observed earlier. 相似文献
103.
The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)-dependent binding of C2 to C4b, and the subsequent cleavage of C2 by C1s or MASP2, respectively. The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement of C2a is similar to Bb, there are certain structural differences. Unexpectedly, the conformation of the metal ion-dependent adhesion site and the position of the alpha7 helix of the vWFA domain indicate a co-factor-bound or open conformation. The active site of the SP domain is in a zymogen-like inactive conformation. On the basis of these structural features, we suggest a model for the initial steps of C3 convertase assembly. 相似文献
104.
The ageing mitochondrial genome 总被引:2,自引:0,他引:2
The population of elderly individuals has increased significantly over the past century and is predicted to rise even more rapidly in the future. Ageing is a major risk factor for many diseases such as neurodegenerative disease, diabetes and cancer. This highlights the importance of understanding the mechanisms involved in the ageing process. One plausible mechanism for ageing is accumulation of mutations in the mitochondrial genome. In this review, we discuss some of the most convincing data surrounding age-related mtDNA mutations and the evidence that these mutations contribute to the ageing process. 相似文献
105.
Thirumangalathu R Krishnan S Bondarenko P Speed-Ricci M Randolph TW Carpenter JF Brems DN 《Biochemistry》2007,46(21):6213-6224
Oxidation of methionine residues is involved in several biochemical processes and in degradation of therapeutic proteins. The relationship between conformational stability and methionine oxidation in recombinant human interleukin-1 receptor antagonist (rhIL-1ra) was investigated to document how thermodynamics of unfolding affect methionine oxidation in proteins. Conformational stability of rhIL-1ra was monitored by equilibrium urea denaturation, and thermodynamic parameters of unfolding (DeltaGH2O, m, and Cm) were estimated at different temperatures. Methionine oxidation induced by hydrogen peroxide at varying temperatures was monitored during "coincubation" of rhIL-1ra with peptides mimicking specific regions of the reactive methionine residues in the protein. The coincubation study allowed estimation of oxidation rates in protein and peptide at each temperature from which normalized oxidation rate constants and activation energies were calculated. The rate constants for buried Met-11 in the protein were lower than for methionine in the peptide with an associated increase in activation energy. The rate constants and activation energy of solvent exposed methionines in protein and peptide were similar. The results showed that conformational stability, monitored using the Cm value, has an effect on oxidation rates of buried methionines. The rate constant of buried Met-11 correlated well with the Cm value but not DeltaGH2O. No correlation was observed for the oxidation rates of solvent-exposed methionines with any thermodynamic parameters of unfolding. The findings presented have implications in protein engineering, in design of accelerated stability studies for protein formulation development, and in understanding disease conditions involving protein oxidation. 相似文献
106.
Richardson TI Norman BH Lugar CW Jones SA Wang Y Durbin JD Krishnan V Dodge JA 《Bioorganic & medicinal chemistry letters》2007,17(13):3570-3574
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe structure-activity relationship studies that led to the discovery of bezopyran 5b. X-ray crystal structures of 5b and a non-selective analog 5c in ERalpha help explain the observed selectivity of the benzopyran platform. 相似文献
107.
Krishnan AV Moreno J Nonn L Malloy P Swami S Peng L Peehl DM Feldman D 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):694-702
Calcitriol, the hormonally active form of Vitamin D, inhibits the growth and development of many cancers through multiple mechanisms. Our recent research supports the contributory role of several new and diverse pathways that add to the mechanisms already established as playing a role in the actions of calcitriol to inhibit the development and progression of prostate cancer (PCa). Calcitriol increases the expression of insulin-like growth factor binding protein-3 (IGFBP-3), which plays a critical role in the inhibition of PCa cell growth by increasing the expression of the cell cycle inhibitor p21. Calcitriol inhibits the prostaglandin (PG) pathway by three actions: (i) the inhibition of the expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the induction of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG receptors that are essential for PG signaling. Since PGs have been shown to promote carcinogenesis and progression of multiple cancers, the inhibition of the PG pathway may add to the ability of calcitriol to prevent and inhibit PCa development and growth. The combination of calcitriol and non-steroidal anti-inflammatory drugs (NSAIDs) result in a synergistic inhibition of PCa cell growth and offers a potential therapeutic strategy. Mitogen activated protein kinase phosphatase 5 (MKP5) is a member of a family of phosphatases that are negative regulators of MAP kinases. Calcitriol induces MKP5 expression in prostate cells leading to the selective dephosphorylation and inactivation of the stress-activated kinase p38. Since p38 activation is pro-carcinogenic and is a mediator of inflammation, this calcitriol action, especially coupled with the inhibition of the PG pathway, contributes to the chemopreventive activity of calcitriol in PCa. Mullerian Inhibiting Substance (MIS) has been evaluated for its inhibitory effects in cancers of the reproductive tissues and is in development as an anti-cancer drug. Calcitriol induces MIS expression in prostate cells revealing yet another mechanism contributing to the anti-cancer activity of calcitriol in PCa. Thus, we conclude that calcitriol regulates myriad pathways that contribute to the potential chemopreventive and therapeutic utility of calcitriol in PCa. 相似文献
108.
Thilakaraj R Raghunathan K Anishetty S Pennathur G 《Bioinformatics (Oxford, England)》2007,23(3):267-271
Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. In this study, we have performed an in silico analysis of metal binding proteins and have identified putative metal binding motifs for the ions of cadmium, cobalt, zinc, arsenic, mercury, magnesium, manganese, molybdenum and nickel. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high-specificity of the motifs. Motifs were also validated against PDB structures and site directed mutagenesis studies. 相似文献
109.
Garver WS Jelinek D Oyarzo JN Flynn J Zuckerman M Krishnan K Chung BH Heidenreich RA 《Journal of cellular biochemistry》2007,101(2):498-516
Niemann-Pick type C1 (NPC1) disease is an autosomal-recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. The NPC1 gene is expressed in every tissue of the body, with liver expressing the highest amounts of NPC1 mRNA and protein. A number of studies have now indicated that the NPC1 protein regulates the transport of cholesterol from late endosomes/lysosomes to other cellular compartments involved in maintaining intracellular cholesterol homeostasis. The present study characterizes liver disease and lipid metabolism in NPC1 mice at 35 days of age before the development of weight loss and neurological symptoms. At this age, homozygous affected (NPC1(-/-)) mice were characterized with mild hepatomegaly, an elevation of liver enzymes, and an accumulation of liver cholesterol approximately four times that measured in normal (NPC1(+/+)) mice. In contrast, heterozygous (NPC1(+/-)) mice were without hepatomegaly and an elevation of liver enzymes, but the livers had a significant accumulation of triacylglycerol. With respect to apolipoprotein and lipoprotein metabolism, the results indicated only minor alterations in NPC1(-/-) mouse serum. Finally, compared to NPC1(+/+) mouse livers, the amount and processing of SREBP-1 and -2 proteins were significantly increased in NPC1(-/-) mouse livers, suggesting a relative deficiency of cholesterol at the metabolically active pool of cholesterol located at the endoplasmic reticulum. The results from this study further support the hypothesis that an accumulation of lipoprotein-derived cholesterol within late endosomes/lysosomes, in addition to altered intracellular cholesterol homeostasis, has a key role in the biochemical and cellular pathophysiology associated with NPC1 liver disease. 相似文献
110.
Krishnan N Vecera J Kodrík D Sehnal F 《Archives of insect biochemistry and physiology》2007,65(3):114-124
Injections of 38 pmol paraquat (1,1'-dimethyl-4,4'-bypyridilium) into adult Pyrrhocoris apterus (average body weight 29.6 mg in males and 36.9 mg in females) caused a significant elevation of lipid peroxidation and protein carbonylation and a decline of membrane fluidity in the microsomal brain fraction. Another manifestation of oxidative stress was a depletion of the reduced glutathione pool and reduction of the gamma-glutamyl transpeptidase activity in the brain extracts. The damaging action of paraquat on the brain was counteracted by simultaneous injection of 1 pmol 20-hydroxyecdysone (20E). 20E restrained lipid peroxidation and the formation of protein carbonyls, ameliorated changes in microsomal membrane fluidity, enhanced the level of reduced glutathione, and upregulated the activity of gamma-glutamyl transpeptidase. At the organismic level, 20E curtailed three detrimental effects caused by paraquat injection: the disappearance of a blood protein, the suppression of fecundity and egg hatchability, and the shortening of adult life span. The data showed that 20E provided a systemic antioxidant protection but the significance of endogenous ecdysteroids in the management of oxidative stress remains to be shown. 相似文献