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61.
We have characterized the biochemical association of two DNA damage-dependent enzymes, poly(ADP-ribose) polymerase-1 (PARP-1) [EC 2.4.2.30] and DNA polymerase beta (pol beta) [2.7.7.7]. We reproducibly observed that pol beta is an efficient covalent target for ADP-ribose polymers under standard conditions of enzymatically catalyzed ADP-ribosylation of betaNAD+ as a substrate. The efficiency of poly(ADP-ribosyl)ation increased as a function of the pol beta and betaNAD+ concentrations. To further characterize the molecular interactions between these two unique polymerases, we also subjected human recombinant PARP-1 to peptide-specific enzymatic degradation with either caspase-3 or caspase-7 in vitro. This proteolytic treatment, commonly referred to as 'a hallmark of apoptosis', generated the two physiologically relevant peptide fragments of PARP-1, e.g., a 24-kDa amino-terminus and an 89-kDa carboxy-terminal domain. Interestingly, co-incubation of the two peptide fragments of PARP-1 with full-length pol beta resulted in their domain-specific molecular association as determined by co-immunoprecipitation and reciprocal immunoblotting. Therefore, our data strongly suggest that, once PARP-1 is proteolyzed by either caspase-3 or caspase-7 during cell death, the specific association of its apoptotic fragments with DNA repair enzymes, such as pol beta, may serve a regulatory molecular role in the execution phase of apoptosis. 相似文献
62.
Ethanolic extract of flowers of Pongamia pinnata was studied for its protective effect against cisplatin and gentamicin induced renal injury in rats. When the extract (300 & 600 mg kg(-1)) was administered orally for 10 days following cisplatin (5 mg kg(-1) i.p.) on day 5, toxicity of cisplatin, as measured by loss of body weight, elevated blood urea and serum creatinine declined significantly. Similarly in gentamicin (40 mg kg(-1) s.c.) induced renal injury, the extract (600 mg kg(-1)) normalized the raised blood urea and serum creatinine levels. Reversal of cisplatin and gentamicin renal cell damage as induced by tubular necrosis ie, marked congestion of the glomeruli with glomerular atrophy, degeneration of tubular epithelial cells with casts in the tubular lumen and infiltration of inflammatory cells in the interstitium was confirmed on histopathological examination. In the preventive regimen, co-administration of the extract with gentamicin significantly prevented the renal injury both functionally and histologically. Ethanolic extract of flowers had a marked nitric oxide free radical scavenging effect, suggesting an antioxidative property. Two flavonoids, known for their antioxidant activity viz. kaempferol and 3, 5, 6, 7, 8-pentamethoxy flavone were isolated from the extract. The results suggested that the flowers of Pongamia pinnata had a protective effect against cisplatin and gentamicin induced renal injury through antioxidant property. 相似文献
63.
Mahapatra PK Mohanty-Hejmadi P Chainy GB 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,131(3):403-410
Vitamin A and its derivatives inhibit normal tail regeneration in amphibians. The most remarkable effect is the development of limbs at the cut end of the tail in anurans. Prior to ectopic limb development, there is an abnormal tail regeneration in the treated tadpoles. The purpose of the present study was to compare oxidative stress condition in the regenerated tail of normal and vitamin A (10I U/ml, 72 h) treated tadpoles. The present findings show a hyper-oxidative stress condition in the regenerated tail of the vitamin A-treated tadpoles of the Indian jumping frog, Polypedates maculatus (Anura: Rhacophoridae). 相似文献
64.
Dhingra G Kumari R Bala S Majumdar S Malhotra S Sharma P Lal S Cullum J Lal R 《Journal of industrial microbiology & biotechnology》2003,30(4):195-204
The genus Amycolatopsis is of industrial importance, as its species are known to produce commercial antibiotics. It belongs to the family Pseudonocardiaceae and has an eventful taxonomic history. Initially strains were identified as Streptomyces, then later as Nocardia. However, based on biochemical, morphological and molecular features, the genus Amycolatopsis, containing seventeen species, was created. The development of molecular genetic techniques for this group has been slow.
The scarcity of molecular genetic tools including stable plasmids, antibiotic resistance markers, transposons, reporter genes,
cloning vectors, and high efficiency transformation protocols has made progress slow, but efforts in the past decade have
led to the development of cloning vectors and transformation methods for these organisms. Some of the cloning vectors have
broad host range (pRL series) whereas others have limited host range (pMEA300 and pMEA100). The cloning vector pMEA300 has
been completely sequenced, while only the minimal replicon (pA-rep) has been sequenced from pRL plasmids. Direct transformation of mycelia and electroporation are the most widely applicable
methods for transforming species of Amycolatopsis. Conjugational transfer from Escherichia coli has been reported only in the species A. japonicum, and gene disruption and replacements using homologous recombination are now possible in some strains.
Electronic Publication 相似文献
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In the present study, we have observed that sialic acid binding protein (SABP – a 54 kDa glycoprotein which was isolated from human endometrial scrapings taken at various stages of the menstrual cycle from normal cycling females and purified to apparent homogeneity and was earlier reported from this laboratory) was found in sufficiently detectable amount in the endometrium of normal cycling women whereas it was found in lesser amount in tissue from women who have recently entered the post-menopause stage. SABP was observed in both follicular and luteal phase of menstrual cycle which was found by western blot analysis. In the de-novo synthesis experiment, synthesis and secretion of SABP was found to be stimulated by estradiol (E2) whereas progesterone (P4) was found to have no significant stimulatory effect on it which was also confirmed by HEC cell culture. In the HEC cell culture, priming of cells with E2 was found to influence the effect of P4 on SABP when it was added 2 h after E2 administration. This was observed by doing immunoprecipitation followed by SDS-PAGE and autoradiography. Hence this report clearly indicates that E2 regulates the synthesis and secretion of 54 kDa SABP from human endometrium. How E2 priming of endometrium influences the effect of P4 on SABP has been discussed. 相似文献
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Pravin L. Kotian Raman Krishnan Scott Rowland Yahya El-Kattan Surendra K. Saini Ramanda Upshaw Shanta Bantia Shane Arnold Y. Sudhakar Babu Pooran Chand 《Bioorganic & medicinal chemistry》2009,17(11):3934-3958
Factor VIIa (FVIIa), a serine protease enzyme, coupled with tissue factor (TF) plays an important role in a number of thrombosis-related disorders. Inhibition of TF·FVIIa occurs early in the coagulation cascade and might provide some safety advantages over other related enzymes. We report here a novel series of substituted biphenyl derivatives that are highly potent and selective TF·FVIIa inhibitors. Parallel synthesis coupled with structure-based drug design allowed us to explore the S2 pocket of the enzyme active site. A number of compounds with IC50 value of <10 nM were synthesized. The X-ray crystal structures of some of these compounds complexed with TF·FVIIa were determined and results were applied to design the next round of inhibitors. All the potent inhibitors were tested for inhibition against a panel of related enzymes and selectivity of 17,600 over thrombin, 450 over trypsin, 685 over FXa, and 76 over plasmin was achieved. Two groups, vinyl 36b and 2-furan 36ab, were identified as the optimum binding substituents on the phenyl ring in the S2 pocket. Compounds with these two substituents are the most potent compounds in this series with good selectivity over related serine proteases. These compounds will be further explored for structure–activity relationship. 相似文献
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