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61.
Yamini P. Ginotra Shefali N. Ramteke Gulshan R. Walke Srikanth Rapole 《Free radical research》2016,50(4):405-413
The binding of metal ions to Aβ peptide plays an important role in the etiology of AD. Copper coordinates chiefly to His residues and produces reactive oxygen species (ROS) upon redox cycling. ROS builds enormous burden on the normal functioning of neuronal cells and results into deleterious effects. Recently, two structurally distinct copper binding sites with contrasting redox properties were characterized. Here, we demonstrate for the first time the effect of binding of two equivalents of Cu2+ on redox properties and cytotoxicity of Aβ peptide. Our electrochemical data and ascorbate consumption assay suggest that in the presence of two equivalents of copper; Aβ peptide has higher propensity of H2O2 generation. The oxidation of Aβ1–16 peptide due to both gamma radiolysis and metal catalyzed oxidation in the presence of two equivalents of copper is inhibited confirming the binding of both equivalents of copper to peptide. The electrochemical and cytotoxicity study shows that negative shift in the reduction potential is reflected as slightly higher cytotoxicity in SH-SY5Y cell lines for Aβ1–16–Cu2+ (1:2) complex. 相似文献
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Falcipain-2, a papain family cysteine protease of the malaria parasite Plasmodium falciparum, plays a key role in parasite hydrolysis of hemoglobin and is a potential chemotherapeutic target. As with many proteases, falcipain-2 is synthesized as a zymogen, and the prodomain inhibits activity of the mature enzyme. To investigate the mechanism of regulation of falcipain-2 by its prodomain, we expressed constructs encoding different portions of the prodomain and tested their ability to inhibit recombinant mature falcipain-2. We identified a C-terminal segment (Leu155–Asp243) of the prodomain, including two motifs (ERFNIN and GNFD) that are conserved in cathepsin L sub-family papain family proteases, as the mediator of prodomain inhibitory activity. Circular dichroism analysis showed that the prodomain including the C-terminal segment, but not constructs lacking this segment, was rich in secondary structure, suggesting that the segment plays a crucial role in protein folding. The falcipain-2 prodomain also efficiently inhibited other papain family proteases, including cathepsin K, cathepsin L, cathepsin B, and cruzain, but it did not inhibit cathepsin C or tested proteases of other classes. A structural model of pro-falcipain-2 was constructed by homology modeling based on crystallographic structures of mature falcipain-2, procathepsin K, procathepsin L, and procaricain, offering insights into the nature of the interaction between the prodomain and mature domain of falcipain-2 as well as into the broad specificity of inhibitory activity of the falcipain-2 prodomain. 相似文献
64.
Kailash Prasad 《Molecular and cellular biochemistry》2010,343(1-2):67-73
Hypercholesterolemia induces oxidative stress, which is known to have adverse effects on the integrity of cells. Hence, hypercholesterolemia may have adverse effects on the hemopoietic system. Vitamin E, an antioxidant, is being used by normo- and hypercholesterolemic subjects. It is, however, not known if vitamin E has any beneficial or adverse effects on the hemopoietic system. The objectives of this study are to determine if (i) hypercholesterolemia has any adverse effects on the hemopoietic system [red blood cell (RBC) count, mean corpuscular volume (MCV), red blood cell distribution width (RDW), hematocrit (Hct), hemoglobin (Hb), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), white blood cell (WBC), and platelet counts, and mean platelet volume (MPV)], and (ii) vitamin E has any effect on the hemopoietic system in hypercholesterolemia. Blood samples were collected before and at various intervals during a high cholesterol diet (0.25% cholesterol) for 2 and 4 months, and while on high cholesterol diet with vitamin E (2 months) following a high cholesterol diet (2 months). Serum cholesterol was measured on an automated Clinical System Analyzer and hemopoietic parameters were measured on an automated Cell-dyn-4000. The results show that hypercholesterolemia decreased RBC count, Hct and Hb, increased MCV, RDW, MCH, and MCHC, and had no effect on WBC and platelet counts, and MPV. Vitamin E did not affect any of the parameters of the hemopoietic system. In conclusion, hypercholesterolemia of short duration has adverse effects on certain elements of the hemopoietic system. Vitamin E does not affect the hemopoietic system during hypercholesterolemia. 相似文献
65.
Abstract Stable reagents were made from nucleoside-phospho-rochloridites and polymeric sec. amines. Treatment of these with tetrazole/CH3CN and transfer of the resulting solution to immobilized oligonucleotide gave 95% chain elongation. 相似文献
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Charles E. Birse Robert J. Lagier William FitzHugh Harvey I. Pass William N. Rom Eric S. Edell Aaron O. Bungum Fabien Maldonado James R. Jett Mehdi Mesri Erin Sult Elizabeth Joseloff Aiqun Li Jenny Heidbrink Gulshan Dhariwal Chad Danis Jennifer L. Tomic Robert J. Bruce Paul A. Moore Tao He Marcia E. Lewis Steve M. Ruben 《Clinical proteomics》2015,12(1)
Background
Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.Results
We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).Conclusions
Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.Electronic supplementary material
The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users. 相似文献68.
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Qazi Mohd Sajid Jamal Mohtashim Lohani Mohd Haris Siddiqui Mohd Haneef Shailendra Kumar Gupta Gulshan Wadhwa 《Bioinformation》2012,8(17):795-800
DNA damage occurs almost all the times in cells, but is repaired also continuously. Occurrence of all these mutations and their
accumulation in one cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA repair mechanism is
hampered. We hypothesize that alterations in DNA repair pathways, either all or at least at one i.e. genetic, translational or posttranslational
level, becomes quite imperative for the initiation and progression of Cancer. Therefore, we investigated the interaction
capability of some carcinogens with the enzymes involved in the DNA repair mechanisms. Cigarette smoke''s derivatives like
NNK and NNAL are well established carcinogens. Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms for
their interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes ranging from +36.96 to -7.47 Kcal/Mol.
Crystal Structure of Human Carbonmonoxy-Haemoglobin at 1.25 Å Resolution, PDB ID-1IRD as a +Ve control, showed
binding energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1, PDB ID- 3CI9 as a -Ve control, showed -
3.91 to +2.09 Kcal/Mol. Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve
control. Study indicated the loss of functions of these enzymes, which probably could be a reason for fettering of DNA repair
pathways resulting in damage accumulation and finally cancer formation. 相似文献