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31.
Hidemitsu Nakajima Takeya Kubo Hideshi Ihara Takatoshi Hikida Teruko Danjo Masatoshi Nakatsuji Neelam Shahani Masanori Itakura Yoko Ono Yasu-Taka Azuma Takashi Inui Atsushi Kamiya Akira Sawa Tadayoshi Takeuchi 《The Journal of biological chemistry》2015,290(23):14493-14503
In addition to its role in DNA repair, nuclear poly(ADP-ribose) polymerase-1 (PARP-1) mediates brain damage when it is over-activated by oxidative/nitrosative stress. Nonetheless, it remains unclear how PARP-1 is activated in neuropathological contexts. Here we report that PARP-1 interacts with a pool of glyceradehyde-3-phosphate dehydrogenase (GAPDH) that translocates into the nucleus under oxidative/nitrosative stress both in vitro and in vivo. A well conserved amino acid at the N terminus of GAPDH determines its protein binding with PARP-1. Wild-type (WT) but not mutant GAPDH, that lacks the ability to bind PARP-1, can promote PARP-1 activation. Importantly, disrupting this interaction significantly diminishes PARP-1 overactivation and protects against both brain damage and neurological deficits induced by middle cerebral artery occlusion/reperfusion in a rat stroke model. Together, these findings suggest that nuclear GAPDH is a key regulator of PARP-1 activity, and its signaling underlies the pathology of oxidative/nitrosative stress-induced brain damage including stroke. 相似文献
32.
Vibha Pandey Yogeshwar Vikram Dhar Parul Gupta Sumit K Bag Neelam Atri Mehar Hasan Asif Prabodh Kumar Trivedi Pratibha Misra 《BMC bioinformatics》2015,16(1)
Background
Sterol glycosyltransferases (SGTs) are ubiquitous but one of the most diverse group of enzymes of glycosyltransferases family. Members of this family modulate physical and chemical properties of secondary plant products important for various physiological processes. The role of SGTs has been demonstrated in the biosynthesis of pharmaceutically important molecules of medicinal plants like Withania somnifera.Results
Analysis suggested conserved behaviour and high similarity in active sites of WsSGTs with other plant GTs. Substrate specificity of WsSGTs were analysed through docking performance of WsSGTs with different substrates (sterols and withanolides). Best docking results of WsSGTL1 in the form of stable enzyme-substrate complex having lowest binding energies were obtained with brassicasterol, transandrosteron and WsSGTL4 with solasodine, stigmasterol and 24-methylene cholesterol.Conclusion
This study reveals topological characters and conserved nature of two SGTs from W. somnifera (WsSGTs) i.e. WsSGTL1 and WsSGTL4. However, besides being ubiquitous in nature and with broad substrate specificity, difference between WsSGTL1 and WsSGTL4 is briefly described by difference in stability (binding energy) of enzyme-substrate complexes through comparative docking.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-015-0563-7) contains supplementary material, which is available to authorized users. 相似文献33.
Over two billion people, depending largely on staple foods, suffer from deficiencies in protein and some micronutrients such as iron and zinc. Among various approaches to overcome protein and micronutrient deficiencies, biofortification through a combination of conventional and molecular breeding methods is the most feasible, cheapest, and sustainable approach. An interspecific cross was made between the wheat cultivar 'Chinese Spring' and Aegilops kotschyi Boiss. accession 396, which has a threefold higher grain iron and zinc concentrations and about 33% higher protein concentration than wheat cultivars. Recurrent backcrossing and selection for the micronutrient content was performed at each generation. Thirteen derivatives with high grain iron and zinc concentrations and contents, ash and ash micronutrients, and protein were analyzed for alien introgression. Morphological markers, high molecular weight glutenin subunit profiles, anchored wheat microsatellite markers, and GISH showed that addition and substitution of homoeologous groups 1, 2, and 7 chromosomes of Ae. kotschyi possess gene(s) for high grain micronutrients. The addition of 1U/1S had high molecular weight glutenin subunits with higher molecular weight than those of wheat, and the addition of 2S in most of the derivatives also enhanced grain protein content by over 20%. Low grain protein content in a derivative with a 2S-wheat translocation, waxy leaves, and absence of the gdm148 marker strongly suggests that the gene for higher grain protein content on chromosome 2S is orthologous to the grain protein QTL on the short arm of group 2 chromosomes. 相似文献
34.
35.
Nica AC Parts L Glass D Nisbet J Barrett A Sekowska M Travers M Potter S Grundberg E Small K Hedman AK Bataille V Tzenova Bell J Surdulescu G Dimas AS Ingle C Nestle FO di Meglio P Min JL Wilk A Hammond CJ Hassanali N Yang TP Montgomery SB O'Rahilly S Lindgren CM Zondervan KT Soranzo N Barroso I Durbin R Ahmadi K Deloukas P McCarthy MI Dermitzakis ET Spector TD;MuTHER Consortium 《PLoS genetics》2011,7(2):e1002003
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits. 相似文献
36.
Farzana Sabir Rajender S. Sangwan Jyoti Singh Laxmi N. Misra Neelam Pathak Neelam S. Sangwan 《Plant biotechnology reports》2011,5(2):127-134
The biotransformation potential of cell suspension cultures generated from Withania somnifera leaf was investigated, using withanolides, i.e. withanolide A, withaferin A, and withanone as precursor substrates. Interestingly,
the cell suspension cultures showed inter-conversion of withanolides, as well converted to some unknown compounds, released
to the culture media. The bio-catalyzed withanolide was detected and quantified by TLC and HPLC, respectively. There is noticeable
conversion of withanolide A to withanone, and vice versa though at a lower level. The type of reaction of this biotransformation
appears to be substitution of 20-OH group to 17-OH in withanolide A. In this paper, we present for the first time the possibility
of biotransformation by inter-conversion of withanolides of pharmacological importance through cell suspension culture of
W. somnifera. The possible role of putative cytochrome P450 hydroxylases is implicated in the conversion. 相似文献
37.
38.
Biosensors for heavy metals 总被引:3,自引:0,他引:3
A biosensor is an analytical device that consists of an immobilized biocomponent in conjunction with a transducer, and represents a synergistic combination of biotechnology and microelectronics. This review summarizes the use of biosensors for detecting and quantifying heavy metal ions. Heavy metal contamination is of serious concern to human health since these substances are non-biodegradable and retained by the ecological system. Conventional analytical techniques for heavy metals (such as cold vapour atomic absorption spectrometry, and inductively coupled plasma mass spectrometry) are precise but suffer from the disadvantages of high cost, the need for trained personnel and the fact that they are mostly laboratory bound. Biosensors have the advantages of specificity, low cost, ease of use, portability and the ability to furnish continuous real time signals. The analysis of heavy metal ions can be carried out with biosensors by using both protein (enzyme, metal-binding protein and antibody)-based and whole-cell (natural and genetically engineered microorganism)-based approaches.Published online: March 2005 相似文献
39.
Malaviya AA Chinoy RF Prabhudesai NM Sawant MH Parmar V Badwe RA 《Acta cytologica》2006,50(3):284-290
OBJECTIVE: To standardize the technique of immunocytochemical (ICC) assessment of estrogen (ER) and progesterone receptor (PR) status in breast cancer by scrape cytology and to compare the results with immunohistochemistry on paraffin blocks. STUDY DESIGN: ICC assessment for ER and PR was done on scrape smears from tissue samples in 200 cases of primary breast cancer. The results were compared to those obtained from immunohistochemical (IHC) evaluation of formalin-fixed paraffin same tissue samples. RESULTS: ER/PR positivity rates as well as staining scores were compared between the scrape smears and tissue sections. The concordance between cytology and histology was 84% for ER and 90% for PR. Both the positivity rates and the staining intensity scores were higher for cytochemistry than for histochemistry. CONCLUSION: The ICC method on scrape smears is a simple test with rapid turnaround time. The sample required is small, and antigen loss due to fixation and processing is minimal. This new method gives a higher yield of hormone receptor positivity and, when used in conjunction with the IHC method, may improve the pickup rate of ER-positive cases, thereby playing an important role in risk stratification and therapeutic decision making in patients with breast cancer. 相似文献
40.
Shahani N Subramaniam S Brandt R 《International journal of biological macromolecules》2006,39(1-3):15-22
Microtubules (MT) are important for cell behavior and maintenance, yet the factors regulating MT assembly in vivo remain obscure. In a biochemical search, we have isolated a small (4.7 kDa) acidic, phosphorylated polypeptide, which we named MINUS (microtubule nucleation suppressor) for its activity to inhibit MT nucleation [P. Fanara, B. Oback, K. Ashman, A. Podtelejnikov, R. Brandt, EMBO J. 18 (1999) 565]. Here, the purification strategy was optimized and the polypeptide purified to homogeneity from bovine brain, Drosophila, Caenorhabditis elegans and yeast. Amino acid analysis showed similar composition of MINUS from different species. In particular, MINUS was rich in glycine, threonine, isoleucine, leucine and acidic amino acids. Inductively coupled plasma mass spectrometry revealed a large peak for phosphorus confirming its identity as a phosphopeptide. For further purification, MINUS was separated as a single peak on reverse phase-HPLC (RP-HPLC). Preliminary sequence analysis suggested MINUS to be N-terminally blocked. However, conventional enzymatic digestions did not reveal differences in the peak profile compared to undigested MINUS. Hence, partial acid hydrolysis and proteinase K digestion was performed followed by RP-HPLC. The proteinase K digested peaks were subjected to Edman degradation (first peak, ser-pro-ser/gly-ser; second peak, tyr/arg-leu), mass spectrometry (no result) and MALDI analysis (no result). Collectively, the data suggest that MINUS belongs to a new class of MT assembly regulators. Sequence information and antibody development will be useful to examine its biological role in a definitive manner. 相似文献