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171.
It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in neurodegenerative
diseases, including Alzheimer’s disease. To find the effective drugs for neurodegenerative diseases, the deep delve into molecular
mechanisms underlie these diseases is necessary. In the current study, we investigated the effects of flavonoid baicalein
on H2O2-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that the treatment of SK-N-MC cells with H2O2 led to a decrease in cell viability through phosphorylation and activation of extracellular signal-regulated kinases (ERKs)
and c-Jun N-terminal kinases (JNKs) pathways followed by increase in Bax/Bcl2 ratio and initiation of caspase-dependent apoptotic
pathways. In addition, our results showed that the exposure of SK-N-MC cells to H2O2 ended up in reduction of glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-glutamyl-cysteine
synthetase (γ-GCS) expression. Our results demonstrated that flavonoid baicalein protected against H2O2-induced cell death by inhibition of JNK/ERK pathways activation and other key molecules in apoptotic pathways, including
blockage of Bax and caspase-9 activation, induction of Bcl-2 expression and prevention of cell death. Baicalein supported
intracellular defense mechanisms through maintaining GSH levels in SK-N-MC cells by the removal of inhibition effects of JNK/ERK
pathways from γ-GCS expression. In addition, baicalein attenuated lipid and protein peroxidation and intracellular reactive
oxygen species in SK-N-MC cells. In accordance with these observations, baicalein can be a promising candidate in antioxidant
therapy and designing of natural-based drug for ROS-induced neurodegenerative disorders. 相似文献
172.
Introduction
Thyroid peroxidase (TPO) gene variations are one cause of thyroid autoimmune diseases. The aim of this study was to examine the association between the T1936C, T2229C and A2257C polymorphisms of the TPO gene and Anti-TPO level.Materials and methods
In this case–control study, 188 individuals (86 males and 102 females), aged 20–80 years, were randomly selected from among the Tehran Lipid and Glucose Study (TLGS) population. A2257C and T2229C SNPs were detected with RFLP by use of BsrI and Eco57I as the restriction enzymes respectively, while the T1936C SNP was determined with ARMS-PCR.Results
In the presence of the C allele of T1936C, Anti-TPO level was significantly increased (CC: 238 ± 43.3, CT: 47.7 ± 15.9, TT: 74.1 ± 11.3 IU/L p = 0.002); however, this association was attenuated after adjustment for sex and age (p = 0.059). No significant difference, before and after adjustment, was found in Anti-TPO level in the presence of T2229C SNP (CC: 129.1 ± 24.5, CT: 43.5 ± 12.6, TT: 126.5 ± 13.8 IU/L p = 0.196). The association between A2257C and Anti-TPO level was only significant after adjustment for potential confounders (p = 0.007). The association between ATC and CTT haplotypes and Anti-TPO level was significant (p = 0.023, 0.021 respectively), the association between CTT and Anti-TPO concentration was also significant after adjustment for sex (p = 0.014).Conclusion
The results of the present study confirmed the association between TPO gene polymorphisms and Anti-TPO level in the Tehranian population. 相似文献173.
Loretta Ma Fumin Dong Maryam Zaid Ashok Kumar Xiaohui Zha 《The Journal of biological chemistry》2012,287(48):40502-40512
Nonresolving inflammatory response from macrophages is a major characteristic of atherosclerosis. Macrophage ABCA1 has been previously shown to suppress the secretion of proinflammatory cytokine. In the present study, we demonstrate that ABCA1 also promotes the secretion of IL-10, an anti-inflammatory cytokine critical for inflammation resolution. ABCA1+/+ bone marrow-derived macrophages secrete more IL-10 but less proinflammatory cytokines than ABCA1−/− bone marrow-derived macrophages, similar to alternatively activated (M2) macrophages. We present evidence that ABCA1 activates PKA and that this elevated PKA activity contributes to M2-like inflammatory response from ABCA1+/+ bone marrow-derived macrophages. Furthermore, cholesterol lowering by statins, methyl-β-cyclodextrin, or filipin also activates PKA and, consequently, transforms macrophages toward M2-like phenotype. Conversely, cholesterol enrichment suppresses PKA activity and promotes M1-like inflammatory response. As the primary function of ABCA1 is cholesterol removal, our results suggest that ABCA1 activates PKA by regulating cholesterol. Indeed, forced cholesterol enrichment in ABCA1-expressing macrophages suppresses PKA activation and elicits M1-like response. Collectively, these findings reveal a novel protective process by ABCA1-activated PKA in macrophages. They also suggest cholesterol lowering in extra-hepatic tissues by statins as an anti-inflammation strategy. 相似文献
174.
The focus of both clinical and basic studies on stem cells is increasing due to their potentials in regenerative medicine and cell-based therapies. Recently stem cells have been genetically modified to enhance an existing character in or to bring a new property to them. However, accomplishment of declared goals requires detailed knowledge about their molecular characteristics which could be achieved by genetic modifications mostly through nonviral transfection strategies. Capable of differentiating into multiple cells, human unrestricted somatic stem cells (hUSSCs) and human mesenchymal stem cells (hMSCs) seem to be suitable candidates for transfection approaches. Involvement of microRNAs (miRNAs) in many biological processes makes their transfection evaluation valuable. Herein we investigated the efficacy and toxicity of four typically used transfection reagents (Arrest-In, Lipofectamine 2000, Oligofectamine and HiPerfect) systematically to deliver fluorescent labeled-miRNA and Green Fluorescent Protein (GFP) expressing plasmid into hUSSCs and hMSCs. The authenticity of stem cells was verified by differentiation experiments along with flow cytometry of surface markers. Our study revealed that stemness properties of these stem cells were not affected by transient transfection. Moreover the ratios of cell viability and transfection efficiency in both analyzed stem cells were reversed. Considering cell viability, the highest fraction of GFP-expressing cells was obtained using Oligofectamine (~50%) while the highest transfection rate of miRNA was achieved by Lipofectamine 2000 (~90%). Moreover dependency of hMSCs to size of transfected nucleic acid and time-dependency of Oligofectamine and their affection on the yield of transfection were observed. Cytotoxicity assessments also showed that hUSSCs are sensitive to HiPerFect. In addition cells treated by Lipofectamine showed morphological changes. Representing the efficient nucleic acid transfection, our research facilitates comprehensive genetic modification of stem cells and demonstrates powerful approaches to understand stem cell molecular regulation mechanisms, which eventually improves nonviral cell-mediated gene therapy.
Electronic supplementary material
The online version of this article (doi:10.1007/s10616-012-9430-9) contains supplementary material, which is available to authorized users. 相似文献175.
176.
Zohreh Habibi Rasool Kheyrabadi Sabrieh Ghasemi Maryam Yousefi Seik Weng Ng 《Phytochemistry letters》2012,5(4):705-707
A new eudesmane-type sesquiterpenoid together with two known flavonoids were isolated from the chloroform extract of the aerial part of Sclerorhachis platyrachis. The structure of the new compound was deduced from its comprehensive spectroscopic analysis including IR, EI-MS, 1H NMR, 13C NMR, DEPT, COSY, HMBC and HMQC and was shown to be 4R*-hydroxy-6S*-tigloyloxyeudesma-7S*-11 (13)-en-12-oic acid (1). Finally, the structure of the new compound was unambiguously confirmed by single-crystal X-ray analysis. The structure of known compounds 2 and 3 were identified by comparison of their spectral data with those reported in the literature. 相似文献
177.
Ghafari M Höger H Keihan Falsafi S Russo-Schlaff N Pollak A Lubec G 《Journal of proteome research》2012,11(3):1891-1896
The NMDA receptor (NMDA-R) is a key element in neural transmission and mediating a vast variety of physiological and pathological processes in the nervous system. It is well-known that phosphorylation is required for functioning of the NMDA-R, and we therefore decided to study this post-translational modification in subunits NR1 and NR2A-D. Immunoprecipitation with an antibody against NR1 was carried out from rat hippocampi and SDS-PAGEs were run. Bands were punched, destained, and digested with trypsin and chymotrypsin and peptides were identified by nano-LC-ESI-MS/MS using an ion trap (HCT). Proteins were identified using specific software. Phosphorylations were verified by phosphatase treatment and reanalysis by mass spectrometry. The NMDA-R subunits NR1 and 2A-D were identified. On NR2A, a novel phosphorylation site was observed at S511, and on NR2B, four novel phosphorylation sites were revealed at S886, S917, S1303, and S1323 by mass spectrometry and verified by phosphatase treatment with mass spectrometrical reanalysis. A series of NMDA-R phosphorylations have been reported and these serve different functions as receptor activation, localization, and protein-protein interactions. Herein, findings of novel phosphorylation sites are extending knowledge on chemical characterization of the NMDA-R and warrant studying function of site-specific receptor phosphorylation in health and disease. 相似文献
178.
One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. In recent years, some researchers have shown that antiviral drugs, such as ritonavir, saquinavir, and nelfinavir, inhibit the growth of over 60 cancer cell lines derived from nine different tumor types. This article studied the anticancer potential of an antiviral drug, lamivudine (LA). The interaction of LA and calf thymus DNA (CT-DNA) was studied using emission, absorption, circular dichroism (CD), and viscosity techniques. The binding constants evaluated from fluorescence data at different temperatures revealed that fluorescence enhancement is a static process that involves complex-DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed ΔH<0 (-126.38±0.61 kJ mol(-1)) and ΔS<0 (-352.17±2.1?J mol(-1) K(-1)); therefore, van der Waals interactions or hydrogen bonds are the main forces in the binding of LA to CT-DNA. The values of K(f) clearly underscore the high affinity of LA to DNA. In addition, detectable changes in the CD spectrum of CT-DNA in the presence of LA indicated conformational changes. All these results showed that groove binding is the binding mode of this drug and CT-DNA. 相似文献
179.
Mahinpour R Riazi G Shokrgozar MA Sarbolouki MN Ahmadian S Douraghi M Hadi Alijanvand H Azadmanesh K Heidari M Naghdi Gheshlaghi Z Moosavi-Movahedi AA 《Cell biology international》2012,36(4):403-408
Arsenical compounds exhibit a differential toxicity to cancer cells. Microtubules are a primary target of a number of anticancer drugs, such as arsenical compounds. The interaction of 1-NAA (1-naphthylarsonic acid) has been investigated on microtubule polymerization under in vitro and cellular conditions. Microtubules were extracted from sheep brain. Transmission electron microscopy was used to show microtubule structure in the presence of 1-NAA. Computational docking method was applied for the discovery of ligand-binding sites on the microtubular proteins. Proliferation of HeLa cells and HF2 (human foreskin fibroblasts) was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay method following their incubation with 1-NAA. Fluorescence microscopic labelling was done with the help of α-tubulin monoclonal antibody and Tunel kit was used to investigate the apoptotic effects of 1-NAA on the HeLa cells. 1-NAA inhibits the tubulin polymerization by the formation of abnormal polymers having high affinity to the inner cell wall. 相似文献
180.
How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC. 相似文献