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Boulares H Zoltoski A Kandan S Akbulut T Yakovlev A Oumouna M 《Biochemical and biophysical research communications》2006,341(2):653-662
A functional relationship between the apoptotic endonuclease DNAS1L3 and the chemotherapeutic drug VP-16 was established. The lymphoma cell line, Daudi, exhibited a significant resistance to VP-16 treatment in comparison to the lymphoma/leukemia cell line, U-937. While U-937 cells degraded their DNA into internucleosomal fragments, Daudi cells failed to undergo such fragmentation in response to the drug. Activation of both caspase-3 and DNA fragmentation factor was not sufficient to trigger internucleosomal DNA fragmentation in Daudi cells. No correlation was found between expression levels of topoisomerase-II, Pgp, Bcl-2, Bax, or Bad and decreased sensitivity of Daudi cells to VP-16. Daudi cells failed to express DNAS1L3 and ectopic expression of this protein significantly sensitized the cells to VP-16. An enhancement of caspase-3 activity and collapse of mitochondrial membrane potential underlie DNAS1L3-mediated sensitization of Daudi cells to VP-16, which may be a direct result of DNAS1L3-mediated increase in PARP-1-activating DNA breaks after VP-16 treatment. Our results suggest that DNAS1L3 plays an active role in lymphoma cell sensitization to VP-16 and that its deficiency may constitute a novel mechanism of drug resistance in these cells. 相似文献
23.
Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression 总被引:2,自引:0,他引:2
Lam SH Wu YL Vega VB Miller LD Spitsbergen J Tong Y Zhan H Govindarajan KR Lee S Mathavan S Murthy KR Buhler DR Liu ET Gong Z 《Nature biotechnology》2006,24(1):73-75
The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype. 相似文献
24.
Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction. 相似文献
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La Porte SL Bollini SS Lanz TA Abdiche YN Rusnak AS Ho WH Kobayashi D Harrabi O Pappas D Mina EW Milici AJ Kawabe TT Bales K Lin JC Pons J 《Journal of molecular biology》2012,421(4-5):525-536
Alzheimer's disease, the most common cause of dementia in the elderly and characterized by the deposition and accumulation of plaques, is composed in part of β-amyloid (Aβ) peptides, loss of neurons, and the accumulation of neurofibrillary tangles. Here, we describe ponezumab, a humanized monoclonal antibody, and show how it binds specifically to the carboxyl (C)-terminus of Aβ40. Ponezumab can label Aβ that is deposited in brain parenchyma found in sections from Alzheimer's disease casualties and in transgenic mouse models that overexpress Aβ. Importantly, ponezumab does not label full-length, non-cleaved amyloid precursor protein on the cell surface. The C-terminal epitope of the soluble Aβ present in the circulation appears to be available for ponezumab binding because systemic administration of ponezumab greatly elevates plasma Aβ40 levels in a dose-dependent fashion after administration to a mouse model that overexpress human Aβ. Administration of ponezumab to transgenic mice also led to a dose-dependent reduction in hippocampal amyloid load. To further explore the nature of ponezumab binding to Aβ40, we determined the X-ray crystal structure of ponezumab in complex with Aβ40 and found that the Aβ40 carboxyl moiety makes extensive contacts with ponezumab. Furthermore, the structure-function analysis supported this critical requirement for carboxy group of AβV40 in the Aβ-ponezumab interaction. These findings provide novel structural insights into the in vivo conformation of the C-terminus of Aβ40 and the brain Aβ-lowering efficacy that we observed following administration of ponezumab in transgenic mouse models. 相似文献
27.
Kollanoor-Johny A Mattson T Baskaran SA Amalaradjou MA Babapoor S March B Valipe S Darre M Hoagland T Schreiber D Khan MI Donoghue A Donoghue D Venkitanarayanan K 《Applied and environmental microbiology》2012,78(8):2981-2987
The efficacies of trans-cinnamaldehyde (TC) and eugenol (EG) for reducing Salmonella enterica serovar Enteritidis colonization in broiler chickens were investigated. In three experiments for each compound, 1-day-old chicks (n = 75/experiment) were randomly assigned to five treatment groups (n = 15/treatment group): negative control (-ve S. Enteritidis, -ve TC, or EG), compound control (-ve S. Enteritidis, +ve 0.75% [vol/wt] TC or 1% [vol/wt] EG), positive control (+ve S. Enteritidis, -ve TC, or EG), low-dose treatment (+ve S. Enteritidis, +ve 0.5% TC, or 0.75% EG), and high-dose treatment (+ve S. Enteritidis, +ve 0.75% TC, or 1% EG). On day 0, birds were tested for the presence of any inherent Salmonella (n = 5/experiment). On day 8, birds were inoculated with ~8.0 log(10) CFU S. Enteritidis, and cecal colonization by S. Enteritidis was ascertained (n = 10 chicks/experiment) after 24 h (day 9). Six birds from each treatment group were euthanized on days 7 and 10 after inoculation, and cecal S. Enteritidis numbers were determined. TC at 0.5 or 0.75% and EG at 0.75 or 1% consistently reduced (P < 0.05) S. Enteritidis in the cecum (≥3 log(10) CFU/g) after 10 days of infection in all experiments. Feed intake and body weight were not different for TC treatments (P > 0.05); however, EG supplementation led to significantly lower (P < 0.05) body weights. Follow-up in vitro experiments revealed that the subinhibitory concentrations (SICs, the concentrations that did not inhibit Salmonella growth) of TC and EG reduced the motility and invasive abilities of S. Enteritidis and downregulated expression of the motility genes flhC and motA and invasion genes hilA, hilD, and invF. The results suggest that supplementation with TC and EG through feed can reduce S. Enteritidis colonization in chickens. 相似文献
28.
Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that its progression can be reduced by the use of hyaluronic acid (HA) or mesenchymal stem cells (MSC). The present study thus aims to examine the effects of MSC, HA and the combination of HA-MSC in treating OA in rat model. The histological observations using O'Driscoll score indicate that it is the use of HA and MSC independently and not their combination that delays the progression of OA. In conclusion, the preliminary study suggest that the use of either HA or MSCs effectively reduces OA progression better than their combined use. 相似文献
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Rahul R Nair Manivasagam B Nandhini Elango Monalisha Kavitha Murugan Thilaga Sethuraman Sangeetha Nagarajan Nayani Surya Prakash Rao Doss Ganesh 《Bioinformation》2012,8(22):1096-1104
Synonymous codon usage of 53 protein coding genes in chloroplast genome of Coffea arabica was analyzed for the first time to find
out the possible factors contributing codon bias. All preferred synonymous codons were found to use A/T ending codons as
chloroplast genomes are rich in AT. No difference in preference for preferred codons was observed in any of the two strands, viz.,
leading and lagging strands. Complex correlations between total base compositions (A, T, G, C, GC) and silent base contents (A3, T3,
G3, C3, GC3) revealed that compositional constraints played crucial role in shaping the codon usage pattern of C. arabica chloroplast
genome. ENC Vs GC3 plot grouped majority of the analyzed genes on or just below the left side of the expected GC3 curve
indicating the influence of base compositional constraints in regulating codon usage. But some of the genes lie distantly below the
continuous curve confirmed the influence of some other factors on the codon usage across those genes. Influence of compositional
constraints was further confirmed by correspondence analysis as axis 1 and 3 had significant correlations with silent base contents.
Correlation of ENC with axis 1, 4 and CAI with 1, 2 prognosticated the minor influence of selection in nature but exact separation
of highly and lowly expressed genes could not be seen. From the present study, we concluded that mutational pressure combined
with weak selection influenced the pattern of synonymous codon usage across the genes in the chloroplast genomes of C. arabica. 相似文献