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61.
Oxidative damage of DNA by chromium(V) complexes: relative importance of base versus sugar oxidation 下载免费PDF全文
Bose RN Moghaddas S Mazzer PA Dudones LP Joudah L Stroup D 《Nucleic acids research》1999,27(10):2219-2226
Chromium(V)-mediated oxidative damage of deoxy-ribonucleic acids was investigated at neutral pH in aqueous solution by utilizing bis(2-ethyl-2-hydroxy-butanato)oxochromate(V) (I) and bis(hydroxyethyl)-amino-tris(hydroxymethyl)methane)oxochromate(V) (II). Single-stranded and double-stranded (ds) calf thymus and human placenta DNA, as well as two oligomers, 5'-GATCTAGTAGGAGGACAAATAGTGTTTG-3' and 5'-GATCCAAGCAAACACTATTTGTCCTCCTACTA-3', were reacted with the chromium(V) complexes. Most products were separated and characterized by chroma-tographic and spectroscopic methods. Polyacrylamide gel electrophoresis experiments reveal more damage at G sites in comparison to other bases. Three primary oxidation products, 5-methylene-2-furanone (5-MF), furfural and 8-oxo-2'-deoxyguanosine, were characterized. A minor product, which appears to be thymine propenal, was also observed. The dsDNA produces more furfural than furanone. The formation of these two products resulted from hydrogen ion or hydride transfer from C1' and C5' positions of the ribose to the oxo-chromium(V) center. Since no enhancements of these products (except propenal) were observed in the presence of oxygen, mechanisms pertaining to the participation of activated oxygen species may be ruled out. The oxidation of the G base is most likely associated with an oxygen atom transfer from the oxo-metallates to the double bond between C8 and N7 of the purine ring. The formation of the propenal may be associated with an oxygen-activated species, since a marginal enhancement of this product was observed in the presence of oxygen. The formation of furfural in higher abundance over 5-MF for dsDNA was attributed to the ease of hydrogen ion (or hydride transfer) from the C5' compared to C1' position of the ribose within a Cr(V)-DNA intermediate in which the metal center is bound to the phosphate diester moiety. 相似文献
62.
Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway 总被引:6,自引:0,他引:6 下载免费PDF全文
Bose A Robida S Furcinitti PS Chawla A Fogarty K Corvera S Czech MP 《Molecular and cellular biology》2004,24(12):5447-5458
Glucose homeostasis is controlled in part by regulation of glucose uptake into muscle and adipose tissue. Intracellular membrane vesicles containing the GLUT4 glucose transporter move towards the cell cortex in response to insulin and then fuse with the plasma membrane. Here we show that the fusion step is retarded by the inhibition of phosphatidylinositol (PI) 3-kinase. Treatment of insulin-stimulated 3T3-L1 adipocytes with the PI 3-kinase inhibitor LY294002 causes the accumulation of GLUT4-containing vesicles just beneath the cell surface. This accumulation of GLUT4-containing vesicles near the plasma membrane prior to fusion requires an intact cytoskeletal network and the unconventional myosin motor Myo1c. Remarkably, enhanced Myo1c expression under these conditions causes extensive membrane ruffling and overrides the block in membrane fusion caused by LY294002, restoring the display of GLUT4 on the cell exterior. Ultrafast microscopic analysis revealed that insulin treatment leads to the mobilization of GLUT4-containing vesicles to these regions of Myo1c-induced membrane ruffles. Thus, localized membrane remodeling driven by the Myo1c motor appears to facilitate the fusion of exocytic GLUT4-containing vesicles with the adipocyte plasma membrane. 相似文献
63.
Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX
penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells.
Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes.
For both proteins, the binding affinity constant decreases, while the possible number of binding sites increases, as the aggregation
state of the porphyrin is increased. The interactions lead to conformational changes of both haemoglobin and myoglobin as
observed in circular dichroism studies. Upon binding with the proteins, protoporphyrin IX releases the heme-bound oxygen from
the oxyproteins, which is dependent on the stoichiometric ratios of the porphyrin: protein. The peroxidase activities of haemoglobin
and myoglobin are potentiated by the protein-porphyrin complexation. Possible mechanisms underlying the relation between the
porphyrin-induced structural modifications of the heme proteins and alterations in their functional properties have been discussed.
The findings may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms
of action as therapeutic agents. 相似文献
64.
Malachite Green (MG), consisting of green crystals with a metallic lustre, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumour promoter. In view of its industrial importance and possible exposure to human beings, MG poses a potential environmental health hazard. We have earlier reported the malignant transformation of Syrian hamster embryo (SHE) cells in primary culture by MG. In this study, we have studied the mitogen activated protein (MAP) kinase signal transduction pathway in preneoplastic cells induced by MG. Western blots of MG induced preneoplastic cells showed no phosphorylation of ERK1, an increased phosphoactive ERK2 associated with a decreased expression of phosphoactive JNK2. However, total forms of ERKs, JNKs and p38 Kinases showed similar levels of expression in control and preneoplastic SHE cells. Indirect immunofluorescence studies have shown a distinct nuclear localisation of phosphoactive ERKs in MG induced preneoplastic cells. Flow cytometric analysis showed an increase of S-phase cells in preneoplastic cells compared to control SHE cells. The present study indicates that hyperphosphorylation of ERK2, decreased JNK2 phosphorylation and an increase in S-phase cells seems to be the early changes associated with the MG induced malignant transformation of SHE cells in primary culture. 相似文献
65.
Bose K Chaudhuri AB 《Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur》2003,61(3):311-321
A cross-sectional study of 279 older (50+ years) urban Bengalee Hindu women was undertaken to study age variations in adiposity, body composition, obesity and central fat distribution. The women were divided into three groups: Group I (G I, 50-59 years), Group II (G II, 60-69 years) and Group III (G III, 70+ years). A significant decreasing age trend was observed in adiposity and body fat composition measures. Women in G I had significantly higher means compared with those in G III. Individuals in G II had intermediate values. However, there was no significant age trend in muscle measures and indices of central body fat distribution. The results revealed that significantly more women in G III (45.8%) were malnourished (BMI < 18.5), while significantly more women in G I (28.7%) were obese (BMI > or = 25). The levels of malnourishment (21.6%) and obesity (24.5%) in G II were intermediate between G I and G III. Age had significant negative correlations with measures of adiposity and body fat composition. Regression analysis revealed that age had significant negative effect on these anthropometric measures. This significant negative impact of age remained even after controlling for the effect of BMI. In conclusion, the present investigation revealed that among older Bengalee Hindu women, there is a significant inverse age trend in adiposity and body fat composition, which is independent of overall adiposity (BMI). However, with ageing, muscle and central body fat distribution remain the same. Furthermore, with increasing age, there is a trend of increasing levels of malnourishment and decreasing levels of obesity. 相似文献
66.
Mishra RS Gu Y Bose S Verghese S Kalepu S Singh N 《The Journal of biological chemistry》2002,277(27):24554-24561
A familial prion disorder with a proline to leucine substitution at residue 102 of the prion protein (PrP(102L)) is typically associated with protease-resistant PrP fragments (PrP(Sc)) in the brain parenchyma that are infectious to recipient animals. When modeled in transgenic mice, a fatal neurodegenerative disease develops, but, unlike the human counterpart, PrP(Sc) is lacking and transmission to recipient animals is questionable. Alternate mice expressing a single copy of PrP(102L) (mouse PrP(101L)) do not develop spontaneous disease, but show dramatic susceptibility to PrP(Sc) isolates from different species. To understand these discrepant results, we studied the biogenesis of human PrP(102L) in a cell model. Here, we report that cells expressing PrP(102L) show decreased expression of the normal 18-kDa fragment on the plasma membrane. Instead, a 20-kDa fragment, probably derived from transmembrane PrP ((Ctm)PrP), accumulates on the cell surface. Because the 20-kDa fragment includes an amyloidogenic region of PrP that is disrupted in the 18-kDa form, increased surface expression of 20-kDa fragment may enhance the susceptibility of these cells to PrP(Sc) infection by providing an optimal substrate, or by amplifying the neurotoxic signal of PrP(Sc). Thus, altered susceptibility of PrP(101L) mice to exogenous PrP(Sc) may be mediated by the 20-kDa (Ctm)PrP fragment, rather than PrP(102L) per se. 相似文献
67.
Interferon regulatory factor 4 contributes to transformation of v-Rel-expressing fibroblasts 总被引:6,自引:0,他引:6 下载免费PDF全文
The avian homologue of the interferon regulatory factor 4 (IRF-4) and a novel splice variant lacking exon 6, IRF-4DeltaE6, were isolated and characterized. Chicken IRF-4 is expressed in lymphoid organs, less in small intestine, and lungs. IRF-4DeltaE6 mRNA, though less abundant than full-length IRF-4, was detected in lymphoid tissues, with the highest levels observed in thymic cells. IRF-4 is highly expressed in v-Rel-transformed lymphocytes, and the expression of IRF-4 is increased in v-Rel- and c-Rel-transformed fibroblasts relative to control cells. The expression of IRF-4 from retrovirus vectors morphologically transformed primary fibroblasts, increased their saturation density, proliferation, and life span, and promoted their growth in soft agar. IRF-4 and v-Rel cooperated synergistically to transform fibroblasts. The expression of IRF-4 antisense RNA eliminated formation of soft agar colonies by v-Rel and reduced the proliferation of v-Rel-transformed cells. v-Rel-transformed fibroblasts produced interferon 1 (IFN1), which inhibits fibroblast proliferation. Infection of fibroblasts with retroviruses expressing v-Rel resulted in an increase in the mRNA levels of IFN1, the IFN receptor, STAT1, JAK1, and 2',5'-oligo(A) synthetase. The exogenous expression of IRF-4 in v-Rel-transformed fibroblasts decreased the production of IFN1 and suppressed the expression of several genes in the IFN transduction pathway. These results suggest that induction of IRF-4 expression by v-Rel likely facilitates transformation of fibroblasts by decreasing the induction of this antiproliferative pathway. 相似文献
68.
N-phthaloyl GABA (P. GABA) inhibited gastric ulceration induced by 3 hr restraint stress at 4 degrees C (CRS) in albino rats. Antiulcer activity of P. GABA was compared with sodium valproate and cimetidine. P. GABA, sodium valproate and cimetidine showed a dose dependent reduction of gastric ulceration. Pretreatment with GABA antagonists-bicuculline methiodide (0.5 mg/kg, im) or 3 mercaptopropionic acid (2 mg/kg, im) reversed the antiulcerogenic activity of both the drugs (P. GABA and sodium valproate). GABA antagonists as such did not induce gastric ulceration in normal rats. 相似文献
69.
Puja Seth Mary Glenshaw Jennifer H. F. Sabatier René Adams Verona Du Preez Nickolas DeLuca Naomi Bock 《PloS one》2015,10(3)
Objectives
To describe alcohol drinking patterns among participants in Katutura, Namibia, and to evaluate brief versions of the AUDIT against the full AUDIT to determine their effectiveness in detecting harmful drinking.Methods
A cross-sectional survey was conducted in four constituencies and 639 participants, 18 years or older, completed a sociodemographic survey and the AUDIT. The effectiveness of the AUDIT-C (first three questions) and the AUDIT-3 (third question) was compared to the full AUDIT.Results
Approximately 40% were identified as harmful, hazardous or likely dependent drinkers, with men having a higher likelihood than women (57.2% vs. 31.0%, p<.0001). Approximately 32% reported making and/or selling alcohol from home. The AUDIT-C performed best at a cutoff ≥ 3, better in men (sensitivity: 99.3%, specificity: 77.8%) than women (sensitivity: 91.7%, specificity: 77.4%). The AUDIT-3 performed poorly (maximum sensitivity: < 90%, maximum specificity: <51%). According to AUROC, the AUDIT-C performed better than the AUDIT-3.Conclusions
A large proportion of participants met criteria for alcohol misuse, indicating a need for screening and referral for further evaluation and intervention. The AUDIT-C was almost as effective as the full AUDIT and may be easier to implement in clinical settings as a routine screening tool in resource-limited settings because of its brevity. 相似文献70.
Swapnil A. Malekar Ashish L. Sarode Alvin C. Bach II Arijit Bose Geoffrey Bothun David R. Worthen 《AAPS PharmSciTech》2015,16(6):1335-1343
This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance (31P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process.KEY WORDS: controlled release, drug combination, liposomes, nanoparticles 相似文献