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1.
Anastasios Karatzas Eirini Giannatou Vassilios Tzortzis Stavros Gravas Evangellos Aravantinos George Moutzouris Michael Melekos Aspasia Tsezou 《Cancer epidemiology》2010,34(3):345-349
Background: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. Patients and methods: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. Results: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P > 0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P = 0.55). Conclusion: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men. 相似文献
2.
《Cellular signalling》2014,26(2):208-219
The p90 ribosomal S6 kinase family (RSK1–4) of Ser/Thr kinases is a downstream component of the Ras-MAPK cascade responsible for regulating various cellular processes. Here, we examined the potential involvement of RSKs in regulating mitosis by transfecting HeLa cells with siRNAs targeting RSK1 and -2, which are the major isoforms. Depletion of RSK1 but not RSK2 triggered a significant accumulation of binucleated cells compared to control cells (0.5% vs. 10.5%, respectively); this was rescued by expression of exogenous RSK1 but not a kinase-defective mutant. Monitoring of cell division by time-lapse imaging revealed that the observed binucleation mainly stemmed from a failure to form and ingress the cleavage furrow during early cytokinesis. Immunocytochemical analysis of RhoA and anillin, the two principal regulators of cleavage furrow formation and ingression, showed that these proteins were abnormally localized during anaphase in RSK1-depleted cells. Furthermore, RSK1-depleted cells seemed to have impairments in midzone microtubule formation, as suggested by morphological changes and lengthening of the midzone (15.2 ± 1.7 μm vs. 17.4 ± 1.7 μm in control cells). We also observed shortening of the pole-to-polar-cortex distance in RSK1-depleted cells (4.30 ± 1.37 μm vs. 2.80 ± 0.84 μm in control cells) and scanty distribution of microtubules at the periphery of the equatorial region during anaphase, suggesting an aberrant distribution of astral microtubules. Taken together, these results suggest that RSK1 is specifically required for cleavage furrow formation and ingression during cytokinesis. This may occur via the involvement of RSK1 in proper midzone and astral microtubule structure formation during anaphase, which is essential for the correct localization of anillin and RhoA. 相似文献
3.
Rita Scarpelli Julia K. Boueres Mauro Cerretani Federica Ferrigno Jesus M. Ontoria Michael Rowley Carsten Schultz-Fademrecht Carlo Toniatti Philip Jones 《Bioorganic & medicinal chemistry letters》2010,20(2):488-492
A potent series of substituted 2-phenyl-2H-indazole-7-carboxamides were synthesized and evaluated as inhibitors of poly (ADP-ribose) polymerase (PARP). This extensive SAR exploration culminated with the identification of substituted 5-fluoro-2-phenyl-2H-indazole-7-carboxamide analog 48 which displayed excellent PARP enzyme inhibition with IC50 = 4 nM, inhibited proliferation of cancer cell lines deficient in BRCA-1 with CC50 = 42 nM and showed encouraging pharmacokinetic properties in rats compared to the lead 6. 相似文献
4.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014,1843(12):2967-2975
Iron accumulation is observed in the substantia nigra of patients with Parkinson's disease. However, it is unknown whether neurotrophic factors, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) participate in the modulation of neuronal iron metabolism. Here, we investigated the effects and underlying mechanisms of BDNF and GDNF on the iron influx process in primary cultured ventral mesencephalic neurons. 6-hydroxydopamine-induced enhanced ferrous iron influx via improper up-regulation of divalent metal transporter 1 with iron responsive element (DMT1 + IRE) was consistently relieved by BDNF and GDNF. Both the mRNA and protein levels of DMT1 + IRE were down-regulated by BDNF or GDNF treatment alone. We further demonstrated the involvement of iron regulatory protein 1 (IRP1) in BDNF- and GDNF-induced DMT1 + IRE expression. Extracellular-regulated kinase 1/2 (ERK1/2) and Akt were activated and participated in these processes. Inhibition of ERK1/2 and Akt phosphorylation abolished the down-regulation of IRP1 and DMT1 + IRE induced by BDNF and GDNF. Taken together, these results show that BDNF and GDNF ameliorate iron accumulation via the ERK/Akt pathway, followed by inhibition of IRP1 and DMT1 + IRE expression, which may provide new targets for the neuroprotective effects of these neurotrophic factors. 相似文献
5.
Magdalena K. Kowalik Dominika Slonina Robert Rekawiecki Jan Kotwica 《Reproductive biology》2013,13(1):15-23
Progesterone (P4) is involved in the regulation of essential reproductive functions affecting the target cells through both nuclear progesterone receptors (PGRs) and membrane progesterone receptors. The aim of this study was to determine the mRNA and protein expression for PGRMC1, PGRMC2, SERBP1 and PGR within the bovine endometrium during the estrous cycle and the first trimester of pregnancy. There were no changes in PGRMC1 and PGRMC2 mRNA and protein expression during the estrous cycle, however, mRNA levels of PGRMC1 and PGRMC2 were increased (P < 0.001) in pregnant animals. SERBP1 mRNA expression was increased (P < 0.05), while the level of this protein was decreased (P < 0.05) on days 11–16 of the estrous cycle. The expression of PGR mRNA was higher (P < 0.01) on days 17–20 compared to days 6–10 and 11–16 of the estrous cycle and pregnancy. PGR-A and PGR-B protein levels were elevated on days 1–5 and 17–20 of the estrous cycle as compared to other stages of the cycle and during pregnancy. In conclusion, our results indicate that P4 may influence endometrial cells through both genomic and nongenomic way. This mechanism may contribute to the regulation of the estrous cycle and provide protection during pregnancy. 相似文献
6.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014,1843(12):2937-2943
Intramuscular creatine plays a crucial role in maintaining skeletal muscle energy homeostasis, and its entry into the cell is dependent upon the sodium chloride dependent Creatine Transporter (CrT; Slc6a8). CrT activity is regulated by a number of factors including extra- and intracellular creatine concentrations, hormones, changes in sodium concentration, and kinase activity, however very little is known about the regulation of CrT gene expression. The present study aimed to investigate how Creatine Transporter (CrT) gene expression is regulated in skeletal muscle. Within the first intron of the CrT gene, we identified a conserved sequence that includes the motif recognized by the Estrogen-related receptor α (ERRα), also known as an Estrogen-related receptor response element (ERRE). Additional ERREs confirming to the known consensus sequence were also identified in the region upstream of the promoter. When partnered with peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1α) or beta (PGC-1β), ERRα induces the expression of many genes important for cellular bioenergetics. We therefore hypothesized that PGC-1 and ERRα could also regulate CrT gene expression and creatine uptake in skeletal muscle. Here we show that adenoviral overexpression of PGC-1α or PGC-1β in L6 myotubes increased CrT mRNA (2.1 and 1.7-fold, P < 0.0125) and creatine uptake (1.8 and 1.6-fold, P < 0.0125), and this effect was inhibited with co-expression of shRNA for ERRα. Overexpression of a constitutively active ERRα (VP16-ERRα) increased CrT mRNA approximately 8-fold (P < 0.05), resulting in a 2.2-fold (P < 0.05) increase in creatine uptake. Lastly, chromatin immunoprecipitation assays revealed that PGC-1α and ERRα directly interact with the CrT gene and increase CrT gene expression. 相似文献
7.
Tadeusz Kaminski Nina Smolinska Anna Nitkiewicz Jadwiga Przala 《Animal reproduction science》2010,117(1-2):111-118
Orexin A and B, also termed hypocretin 1 and 2, are associated with the stimulation of food intake and arousal. The biological actions of the hormones are mediated via two distinct G protein-coupled receptors, termed orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). OX1R is selective for orexin A and OX2R binds orexin A and orexin B with similar affinity. The present study analyzed mRNA and protein expressions of OX1R and OX2R in adenohypophysis (AP) and neurohypophysis (NP) of cycling pigs. The tissue samples were harvested on days 2–3, 10–12, 14–16, and 17–19 of the oestrous cycle. Using quantitative real-time PCR higher OX1R gene expression was detected in AP on days 2–3 relative to days 10–12, 14–16 and 17–19 (p < 0.05). In NP the OX1R mRNA level was elevated on days 10–12 compared to the remaining stages (p < 0.05). OX2R gene expression in AP was the lowest on days 10–12 (p < 0.05 compared to days 2–3 and 17–19) and the expression peak occurred on days 17–19 (p < 0.05 vs. the all studied stages). In NP the highest (p < 0.05) expression of OX2R mRNA was noted on days 17–19 in relation to the remaining periods. OX1R protein content in AP was greatest on days 10–12 (p < 0.05), whereas in NP it was greatest on days 2–3 and 14–16 (p < 0.05 vs. days 10–12 and 17–19). In both cases the lowest OX1R protein expression was observed during follicular phase (p < 0.05 in relation to three remaining studied stages). OX2R protein in AP was lower (p < 0.05) on days 2–3 and 14–16 compared to days 10–12 and 17–19. In NP the lowest (p < 0.05) expression of this protein was on days 17–19 and the highest on days 10–12 (p < 0.05 compared to days 2–3 and 17–19). In summary, the present findings provide the first evidence that OX1R and OX2R mRNAs and proteins occur in the pituitary of the pig and indicate the dependence of orexin receptor expression on the endocrine reproductive state. 相似文献
8.
Mehrdad Rajaei Iraj Saadat Mostafa Saadat 《Biochemical and biophysical research communications》2013,430(2):640-641
Polymorphism of variable number of tandem repeats (VNTR) in the promoter region of X-ray repair cross-complementing 5 (MIM: 194364, XRCC5; rs6147172) was reported. The aim of the present study is to evaluate the influence of this polymorphism on XRCC5 mRNA levels. Genotypes of XRCC5 VNTR were determined by high resolution of melting analysis (HRMA). The quantitative XRCC5 mRNA expression (compared to ß-actin expression) among 0R/1R, 1R/2R, and 1R/3R genotypes was investigated. There was a negative correlation between the overall number of tandem repeats and XRCC5 expression (r = ?0.965, df = 7, P < 0.001). The mRNA level of XRCC5 decreased as function of number of tandem repeats. The 3R allele of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression. 相似文献
9.
Jguirim-Souissi Imen Ludivine Billiet Clarisse Cuaz-Pérolin Nadège Michaud Mustapha Rouis 《Free radical biology & medicine》2009,46(10):1404-1410
In a previous study, we identified the regulated in development and DNA damage response 2 (REDD2) gene as a highly expressed gene in human atherosclerotic lesions in comparison to normal artery, as well as in cultured human macrophages, and showed its implication in oxidized low-density lipoprotein (LDL)-induced macrophage death sensitivity. In this article, we attempt to identify the mechanism by which REDD2 induces such a phenomenon. Transient transfection of U-937 monocytic cells with a pCI.CMV.REDD2 expression vector increased by approximately twofold the mRNA levels of REDD2 in comparison to control cells transfected with pCI.CMV.GFP. Reactive oxygen species (ROS) production was significantly induced in REDD2-transfected cells compared with control cells (157 ± 48 and 100 ± 8 arbitrary units/mg cell protein, respectively; p < 0.05). Moreover, a significant increase in parameters known to reflect the oxidative modifications of LDL was observed. Among enzymes involved in ROS production or degradation, we found a specific reduction in thioredoxin-1 (Trx-1) mRNA (~ 52 ± 7% decrease, p < 0.01 vs control cells) and protein (~ 60 ± 4% decrease, p < 0.001 vs control cells) levels in cells overexpressing REDD2 in comparison to control cells. In contrast, transfection of U-937 cells with siRNA against REDD2 decreased the mRNA levels of REDD2 by ~ 60% and increased Trx-1 mRNA and protein levels. Moreover, we observed no or a moderate increase in Bax (proapoptotic) and a significant decrease in Bcl2 (antiapoptotic) gene expression in cells that overexpress REDD2 compared to control cells. In addition, we showed that Trx-1 mRNA and protein levels were increased at low H2O2 doses and decreased at higher doses. Interestingly, macrophages isolated from human atherosclerotic lesions differentially express REDD2 and Trx-1. Indeed, in certain patients, levels of REDD2 mRNA were low and those of Trx-1 mRNA were high. In contrast, in other patients, levels of REDD2 were high and levels of Trx-1 mRNA were low. 相似文献
10.
Reactive oxygen species (ROS) are strong inducers of the angiogenic hormone vascular endothelial growth factor (VEGF). Although, rutin (R) in combination with vitamin E (VE) has been shown to synergistically inhibit oxidative damage, it is unclear whether the combination of R and VE (R + VE) inhibits VEGF secretion in tumor cells. Using a human promyelocytic leukemia (HL-60) cell line, we showed that R in combination with VE synergistically decreased the expressions of VEGF protein and mRNA. We also demonstrated that R + VE significantly decreased the binding capacity of nuclear factor-activator protein-1 (AP-1) to the VEGF gene promoter and decreased the expression of c-Jun protein. Furthermore, we demonstrated that R + VE synergistically reduced insulin receptor substrate-1 (IRS-1) protein expression in HL-60 cells. The decrease of ROS was only partially associated with the decrease of VEGF secreted (r2 = 0.12, P = 0.083). Thus, the present results indicate that R in combination with VE attenuates VEGF expression in HL-60 cells and that this effect is mediated by a decreased binding activity of AP-1 through down-regulation of protein expression of insulin-like growth factor 1 receptor (IGF1-R)/IRS-1, while the antioxidant activity of R + VE appears to play a minor role. 相似文献
11.
Folate deficiency contributes to impaired adult hippocampal neurogenesis, yet the mechanisms remain unclear. Here we use HT-22 hippocampal neuron cells as model to investigate the effect of folate deprivation (FD) on cell proliferation and apoptosis, and to elucidate the underlying mechanism. FD caused cell cycle arrest at G0/G1 phase and increased the rate of apoptosis, which was associated with disrupted expression of folate transport and methyl transfer genes. FOLR1 and SLC46A1 were (P < 0.01) down-regulated, while SLC19A1 was up-regulated (P < 0.01) in FD group. FD cells exhibited significantly (P < 0.05) higher protein content of BHMT, MAT2b and DNMT3a, as well as increased SAM/SAH concentrations and global DNA hypermethylation. The expression of the total and all the 3 classes of IGF-1 mRNA variants was significantly (P < 0.01) down-regulated and IGF-1 concentration was decreased (P < 0.05) in the culture media. IGF-1 signaling pathway was also compromised with diminished activation (P < 0.05) of STAT3, AKT and mTOR. CpG hypermethylation was detected in the promoter regions of IGF-1 and FOLR1 genes, while higher SLC19A1 mRNA corresponded to hypomethylation of its promoter. IGF-1 supplementation in FD media significantly abolished FD-induced decrease in cell viability. However, IGF-1 had limited effect in rescuing the cell phenotype when added 24 h after FD. Taken together, down-regulation of IGF-1 expression and signaling is involved in FD-induced cell cycle arrest and apoptosis in HT-22 hippocampal neuron cells, which is associated with an abnormal activation of methyl transfer pathway and hypermethylation of IGF-1 gene promoter. 相似文献
12.
Y.S. Weems T.M. Nett L.A. Rispoli T.L. Davis D.L. Johnson T. Uchima A. Raney E. Lennon J. Pang T. Harbert G. Bowers K. Goto A. Ong N. Tsutahara R.D. Randel C.W. Weems 《Prostaglandins & other lipid mediators》2010,91(1-2):42-50
Loss of luteal progesterone secretion at the end of the ovine estrous cycle is via uterine PGF2α secretion. However, uterine PGF2α secretion is not decreased during early pregnancy in ewes. Instead, the embryo imparts a resistance to PGF2α. Prostaglandins E (PGE; PGE1 + PGE2) are increased in endometrium and uterine venous blood during early pregnancy in ewes to prevent luteolysis. Chronic intrauterine infusion of PGE1 or PGE2 prevents spontaneous or IUD, estradiol-17β, or PGF2α-induced premature luteolysis in nonbred ewes. The objective was to determine whether chronic intrauterine infusion of PGE1 or PGE2 affected mRNA for LH receptors, occupied and unoccupied receptors for LH in luteal and caruncular endometrium, and luteal function. Ewes received Vehicle, PGE1, or PGE2 every 4 h from days 10 to 16 of the estrous cycle via a cathether installed in the uterine lumen ipsilateral to the luteal-containing ovary.Jugular venous blood was collected daily for analysis of progesterone and uterine venous blood was collected on day-16 for analysis of PGF2α and PGE. Corpora lutea and caruncular endometrium were collected from day-10 preluteolytic control ewes and day-16 ewes treated with Vehicle, PGE1 or PGE2 for analysis of the mRNA for LH receptors and occupied and unoccupied receptors for LH. Luteal weights on day-16 in ewes treated with PGE1 or PGE2 and day-10 control ewes were similar (P ≥ 0.05), but were greater (P ≤ 0.05) than in day-16 Vehicle-treated ewes. Progesterone profiles on days 10–16 differed (P ≤ 0.05) among treatment groups: PGE1 > PGE2 > Vehicle-treated ewes. Concentrations of PGF2α and PGE in uterine venous plasma on day-16 were similar (P ≥ 0.05) in the three treatment groups. Luteal mRNA for LH receptors and unoccupied and occupied LH receptors were similar (P ≥ 0.05) in day-10 control ewes and day-16 ewes treated with PGE2 and were lower (P ≤ 0.05) in day-16 Vehicle-treated ewes. PGE2 prevented loss (P ≤ 0.05) of day-16 luteal mRNA for LH receptors and occupied and unoccupied LH receptors. Luteal and caruncular tissue mRNA for LH receptors and occupied and unoccupied LH receptors were greater (P ≤ 0.05) on day-16 of PGE1-treated ewes than any treatment group. mRNA for LH receptors and occupied and unoccupied receptors for LH in caruncules were greater (P ≤ 0.05) in day-16 Vehicle or PGE2-treated ewes than in day-10 control ewes. It is concluded that PGE1 and PGE2 share some common mechanisms to prevent luteolysis; however, only PGE1 increased luteal and endometrial mRNA for LH receptors and occupied and unoccupied LH receptors. PGE2 prevents a decrease in luteal mRNA for LH receptors and occupied and unoccupied receptors for LH without altering endometrial mRNA for LH receptors or occupied and unoccupied receptors for LH. 相似文献
13.
Wint Nandar Elizabeth B. Neely Erica Unger James R. Connor 《生物化学与生物物理学报:疾病的分子基础》2013,1832(6):729-741
Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. 相似文献
14.
Allograft inflammatory factor-1 (AIF-1), an interferon (IFN)-γ-inducible calcium-binding cytokine, is associated with the inflammatory response and defense. We cloned and analyzed the expression pattern of the AIF-1 gene of the pearl oyster Pinctada martensii, hereafter designated PmAIF-1. The full-length PmAIF-1 cDNA is 946 bp in length and consists of a 5′-untranslated region (UTR) of 120 bp, a 3′-UTR of 376 bp, and an open reading frame (ORF) of 450 bp encoding a polypeptide of 149 amino acids with an estimated molecular mass of 17 kDa. Sequence analysis reveals that PmAIF-1 contains two EF hand Ca+2-binding motifs like those in previously characterized AIF-1s while alignment with known AIF-1 protein sequences reveals higher similarity to invertebrate orthologs than to those of vertebrates.Quantitative PCR analysis reveals that PmAIF-1 is constitutively expressed, with the highest expression detected in hemocytes, and the expression level of PmAIF-1 mRNA was significantly up-regulated in hemocytes, gill, digestive gland under bacterial challenge and tissue injury. After challenged by gram-negative bacteria Vibrio alginolyticus and Vibrio parahaemolyticus, gram-positive bacteria Bacillus subtilis, the expression level of this gene in hemocytes were all up-regulated and reached the maximum point at 12 h (5.80 folds, P < 0.01), 6 h (5.02 folds, P < 0.01) and 12 h (5.49 folds, P < 0.01), respectively. Under shell damage and mantle injury, PmAIF-1 mRNA increased gradually in the first 3 h and reached a peak of expression at 6 h post-injury. These findings suggest that PmAIF-1 is an acute-response protein involved in the innate immune responses of pearl oysters, and provide general information about the mechanisms of innate immune defense against bacterial infection in pearl oysters. 相似文献
15.
《Bioorganic & medicinal chemistry》2014,22(17):4948-4954
The anti-growth effect of a palladium(II) complex—[PdCl(terpy)](sac)·2H2O] (sac = saccharinate, and terpy = 2,2′:6′,2″-terpyridine)—was tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in vivo. The mode of cell death was determined by both histological and biochemical methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the palladium(II) saccharinate complex of terpyridine represents a potentially active novel complex for the breast cancer treatment, thus warrants further studies. 相似文献
16.
Shimaa M. Abdel-Salam M.U. Dahot A.S. Sadik 《Journal of Genetic Engineering and Biotechnology》2012,10(1):55-65
We are reporting a molecular comparative analysis of component 1 BBTV-DNA-R of an Egyptian isolate of (BBTV) and 30 different geographical isolates. DNA was extracted from BBTV-infected adult banana aphids collected from El-Qalubia Governorate, Egypt. Using specific primers the BBTV-DNA-R was amplified, cloned into a prokaryote vector, sequenced and a molecular comparative analysis of BBTV-DNA-R of this study and some overseas isolates of BBTV-infected banana plants was determined. Results showed that the component 1 consists of 1108 nts and contains a sequence of 69 nts representing the CR-SL of 31 nts. A CR-M (90 nts) at the position (972–1062) characterized with GC-rich sequence from nts 76 to 90 (average of 80% G + C) was found. Alignment results of BBTV DNA-R confirmed the presence of a number of conserved regions in all isolates. Large ORF of 861 nts at position 102 to 962 in the virion sense were detected. The predicted protein of this ORF consisted of 286 amino acids and had a molecular weight of 33.8 kDa. The DNA-phylogenetic analysis showed a percent identity of 98.0 and 97.9 between BBTV DNA-R and isolates of Pakistan (isolate TJ1) and Australia (isolate V1), respectively. The similarities between the gene product of Egyptian BBTV DNA-R and the 30 overseas isolates ranged from 93.7 to 99.0%. Differences in phylogenetic trees based on the entire sequence of BBTV DNA-R, CR-M and amino acid sequences confirmed the existence of two taxonomic groups of BBTV and the Egyptian isolate belongs to the south pacific group. 相似文献
17.
《Cytokine》2016
BackgroundTransforming growth factor-beta 1 (TGF-β1), a multifunctional cytokine, acts as a key factor for Epstein-Barr virus (EBV) reactivation. We investigated the role of TGF-β1 in latent and lytic stages of EBV in relation to Helicobacter pylori infection among patients with gastric cancer (GC) and peptic ulcer disease (PUD).MethodGastric mucosal TGF-β1 expression was determined in 95 EBV positive patients with gastroduodenal pathology [GC 40, PUD 19 and non-ulcer dyspepsia (NUD) 36] by quantitative real time PCR. Presence of H. pylori infection was diagnosed when either culture or any two of three tests (RUT, histopathology and specific ureA PCR) were positive. Serum level of TGF-β1 was detected among 60 patients using ELISA.ResultsMucosal TGF-β1 mRNA expression was detected in 85 of 95 EBV positive patients and it was significantly higher in patients with GC (p = 0.042). TGF-β1 expression tended to be higher among H. pylori non-infected than infected patients (3.80 ± 6.24 vs. 2.07 ± 2.50, p = 0.085). Both mRNA and serum level had significant association with lytic stage of EBV in absence of H. pylori infection when compared with its presence (5.21 ± 4.00 vs. 2.29 ± 2.89, p = 0.040 and 842.00 [669.55] vs. 662.63 [628.76], p = 0.049; respectively).ConclusionTGF-β1 expression was significantly associated with GC. TGF-β1 was higher both at expression and translational levels in lytic EBV infection without H. pylori suggests that H. pylori infection might play important role in preventing EBV reactivation through attenuated TGF-β1 expression. This might be a “wise host defense against EBV reactivation”. 相似文献
18.
Hanna Shevalye Yury Maksimchyk Pierre Watcho Irina G. Obrosova 《生物化学与生物物理学报:疾病的分子基础》2010,1802(11):1020-1027
Poly(ADP-ribose)polymerase (PARP) inhibitors prevent or alleviate diabetic nephropathy. This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse. PARP-1?/? and the wild-type (129S1/SvImJ) mice were made diabetic with streptozotocin, and were maintained for 12 weeks. Final blood glucose concentrations were increased ~ 3.7-fold in both diabetic groups. PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative. PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression. Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β1 accumulations (both by ELISA) were slightly lower in diabetic PARP-1?/? mice, but the differences with diabetic wild-type group did not achieve statistical significance. In conclusion, PARP-1?/? gene deficiency alleviates although does not completely prevent diabetic kidney disease. 相似文献
19.
Hemochromatosis is the most common hereditary disorder in the Nordic population, if left untreated it can result in severe parenchymal iron accumulation. Bloodletting is mainstay treatment. Iron and trace elements partially share cellular uptake and transport mechanisms, and the aim of the present study was to see if bloodletting for hemochromatosis affects trace elements homeostasis. We recruited patients referred for diagnosis and treatment of hemochromatosis, four women and 22 men 23–68 years of age. Thirteen were C282Y homozygote, one was C282Y heterozygote, three were H63D homozygote, seven were compound heterozygote and two had none of the mutations above. Iron and liver function tests were performed; serum levels of trace elements were measured using inductively coupled plasma mass spectrometry. Results before the start of treatment and after normalization of iron parameters were compared. On completion of the bloodlettings the following average serum concentrations increased: Co from 5.6 to 11.5 nmol/L, serum Cu 16.2–17.6 μmol/L, Ni increased from 50.0 to 52.6 nmol/L and Sb from 13.2 to 16.3 nmol/L. Average serum Mn concentration declined from 30.2 to 28.3 nmol/L. All changes were statistically significant (by paired t-test). B, Ba, Cs, Mo, Se, Sr and Zn were not significantly changed. We conclude that bloodlettings in hemochromatosis lead to changes in trace element metabolism, including increased absorption of potentially toxic elements. 相似文献
20.
Michael D. Dennis Nora K. McGhee Leonard S. Jefferson Scot R. Kimball 《Cellular signalling》2013,25(12):2709-2716