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Int. J. Mol. Sci., Volume 15, Issue 6 (June 2014), Pages 9173-11203

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Open AccessArticle A-769662 Protects Osteoblasts from Hydrogen Dioxide-Induced Apoptosis through Activating of AMP-Activated Protein Kinase (AMPK)
Int. J. Mol. Sci. 2014, 15(6), 11190-11203; https://doi.org/10.3390/ijms150611190
Received: 17 March 2014 / Revised: 14 April 2014 / Accepted: 4 May 2014 / Published: 23 June 2014
Cited by 20 | PDF Full-text (1844 KB) | HTML Full-text | XML Full-text
Abstract
Here we report that 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist A-769662 inhibited hydrogen peroxide (H2O2)-induced viability loss and apoptosis of human and mouse osteoblast cells. H2O2-induced moderate AMPK activation in osteoblast cells, which was enhanced
[...] Read more.
Here we report that 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist A-769662 inhibited hydrogen peroxide (H2O2)-induced viability loss and apoptosis of human and mouse osteoblast cells. H2O2-induced moderate AMPK activation in osteoblast cells, which was enhanced by A-769662. Inactivation of AMPK by its inhibitor compound C, or by target shRNA-mediated silencing and kinase dead (KD) mutation exacerbated H2O2-induced cytotoxicity in osteoblast cells. A-769662-mediated protective effect against H2O2 was also blocked by AMPK inhibition or depletion. A-769662 inhibited reactive oxygen species (ROS) accumulation by H2O2 in osteoblast cells. Meanwhile, H2O2-induced ATP depletion was inhibited by A-769662, but was aggravated by compound C. Further, H2O2 induced AMPK-dependent and pro-survival autophagy in cultured osteoblast cells, which was enhanced by A-769662. Our results suggested that activation of AMPK by H2O2 is anti-apoptosis and pro-survival in osteoblast cells, probably due to its anti-oxidant, pro-autophagy and ATP preservation abilities, and A-769662-mediated cell-protective effect in osteoblast cells requires AMPK activation. Our study suggests that A-769662 might be further investigated as a novel anti-osteonecrosis agent. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle Generation and Analysis of Expressed Sequence Tags (ESTs) from Halophyte Atriplex canescens to Explore Salt-Responsive Related Genes
Int. J. Mol. Sci. 2014, 15(6), 11172-11189; https://doi.org/10.3390/ijms150611172
Received: 20 May 2014 / Revised: 11 June 2014 / Accepted: 12 June 2014 / Published: 23 June 2014
Cited by 8 | PDF Full-text (711 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Little information is available on gene expression profiling of halophyte A. canescens. To elucidate the molecular mechanism for stress tolerance in A. canescens, a full-length complementary DNA library was generated from A. canescens exposed to 400 mM NaCl, and provided 343
[...] Read more.
Little information is available on gene expression profiling of halophyte A. canescens. To elucidate the molecular mechanism for stress tolerance in A. canescens, a full-length complementary DNA library was generated from A. canescens exposed to 400 mM NaCl, and provided 343 high-quality ESTs. In an evaluation of 343 valid EST sequences in the cDNA library, 197 unigenes were assembled, among which 190 unigenes (83.1% ESTs) were identified according to their significant similarities with proteins of known functions. All the 343 EST sequences have been deposited in the dbEST GenBank under accession numbers JZ535802 to JZ536144. According to Arabidopsis MIPS functional category and GO classifications, we identified 193 unigenes of the 311 annotations EST, representing 72 non-redundant unigenes sharing similarities with genes related to the defense response. The sets of ESTs obtained provide a rich genetic resource and 17 up-regulated genes related to salt stress resistance were identified by qRT-PCR. Six of these genes may contribute crucially to earlier and later stage salt stress resistance. Additionally, among the 343 unigenes sequences, 22 simple sequence repeats (SSRs) were also identified contributing to the study of A. canescens resources. Full article
(This article belongs to the Special Issue Metagenomics: a Powerful Lens Viewing the Microbial World)
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Open AccessArticle Genetic Variations of TAP1 Gene Exon 3 Affects Gene Expression and Escherichia coli F18 Resistance in Piglets
Int. J. Mol. Sci. 2014, 15(6), 11161-11171; https://doi.org/10.3390/ijms150611161
Received: 12 April 2014 / Revised: 22 May 2014 / Accepted: 27 May 2014 / Published: 20 June 2014
Cited by 6 | PDF Full-text (945 KB) | HTML Full-text | XML Full-text
Abstract
Firstly, our research group identified Sutai pigs’ phenotypes that exhibited extreme resistance and susceptibility to the Escherichia coli F18 respectively, and then eight ETEC (Enterotoxigenic Escherichia coli) F18-resistant piglets and eight ETEC F18-sensitive piglets were selected. Then, the TAP1 (
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Firstly, our research group identified Sutai pigs’ phenotypes that exhibited extreme resistance and susceptibility to the Escherichia coli F18 respectively, and then eight ETEC (Enterotoxigenic Escherichia coli) F18-resistant piglets and eight ETEC F18-sensitive piglets were selected. Then, the TAP1 (Transporter associated with antigen processing) mRNA relative expression levels were analyzed in 11 tissues of the resistant and susceptible phenotypes. Simultaneously, we detected the genetic variations in exon 3 of the TAP1 gene and evaluated the TAP1 mRNA expression levels among the different genotype pigs to study the effects of the genetic variation on gene expression, and the E. coli F18 resistance. The results revealed higher expression levels in the resistant genotypes than that in the susceptible genotypes in 11 tissues, with significant differences in the spleen, lymph node, lung, thymus, duodenum and jejunum. Furthermore, a G729A mutation was identified in the TAP1 gene exon 3, and this mutation deviates from Hardy-Weinberg equilibrium (p < 0.01). The TAP1 mRNA levels in GG genotype were significantly higher than that in the other two genotypes, with significant differences in the liver, lung, kidney, thymus, lymph node, duodenum and jejunum tissues. We speculated that high expression of the TAP1 gene might confer resistance against the E. coli F18, the G729A mutation had a significant effect on the mRNA expression, and individuals with the GG genotype possessed a stronger ability to resist the E. coli F18 infection. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessReview Identification of Drivers from Cancer Genome Diversity in Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(6), 11142-11160; https://doi.org/10.3390/ijms150611142
Received: 2 April 2014 / Revised: 12 June 2014 / Accepted: 16 June 2014 / Published: 20 June 2014
Cited by 15 | PDF Full-text (431 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers with a dismal outcome. The complicated molecular pathogenesis of HCC caused by tumor heterogeneity makes it difficult to identify druggable targets useful for treating HCC patients. One approach that has a potential for
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Hepatocellular carcinoma (HCC) is one of the most common cancers with a dismal outcome. The complicated molecular pathogenesis of HCC caused by tumor heterogeneity makes it difficult to identify druggable targets useful for treating HCC patients. One approach that has a potential for the improvement of patient prognosis is the identification of cancer driver genes that play a critical role in the development of HCC. Recent technological advances of high-throughput methods, such as gene expression profiles, DNA copy number alterations and somatic mutations, have expanded our understanding of the comprehensive genetic profiles of HCC. Integrative analysis of these omics profiles enables us to classify the molecular subgroups of HCC patients. As each subgroup classified according to genetic profiles has different clinical features, such as recurrence rate and prognosis, the tumor subclassification tools are useful in clinical practice. Furthermore, a global genetic analysis, including genome-wide RNAi functional screening, makes it possible to identify cancer vulnerable genes. Identification of common cancer driver genes in HCC leads to the development of an effective molecular target therapy. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Open AccessArticle TRAF6 Inhibition Rescues Dexamethasone-Induced Muscle Atrophy
Int. J. Mol. Sci. 2014, 15(6), 11126-11141; https://doi.org/10.3390/ijms150611126
Received: 2 May 2014 / Revised: 2 June 2014 / Accepted: 5 June 2014 / Published: 20 June 2014
Cited by 9 | PDF Full-text (2878 KB) | HTML Full-text | XML Full-text
Abstract
Tumor necrosis factor receptor-associated factor 6 (TRAF6), a unique E3 ubiquitin ligase and adaptor protein, is involved in activation of various signaling cascades. Recent studies identify TRAF6 as one of the novel regulators of skeletal muscle atrophy. The role of TRAF6 in glucocorticoid-induced
[...] Read more.
Tumor necrosis factor receptor-associated factor 6 (TRAF6), a unique E3 ubiquitin ligase and adaptor protein, is involved in activation of various signaling cascades. Recent studies identify TRAF6 as one of the novel regulators of skeletal muscle atrophy. The role of TRAF6 in glucocorticoid-induced muscle atrophy, however, remains to be elucidated. In this study, we show that TRAF6 and its downstream signaling molecules, muscle atrophy F-box (MAFBx) and muscle ring finger 1 (MuRF1), were all upregulated in dexamethasone-induced atrophy of mouse C2C12 myotubes or mouse tibialis anterior (TA) muscle. To further investigate the role of TRAF6 in dexamethasone-induced muscle atrophy, TRAF6-siRNA was used to transfect cultured C2C12 myotubes or was injected into the TA muscle of mice respectively, and we note that TRAF6 knockdown attenuated dexamethasone-induced muscle atrophy in vitro and in vivo, and concomitantly decreased the expression of MuRF1 and MAFBx. Our findings suggest that a decreased expression of TRAF6 could rescue dexamethasone-induced skeletal muscle atrophy through, at least in part, regulation of the expression of MAFBx and MuRF1. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle New Dihydro-β-agarofuran Sesquiterpenes from Parnassia wightiana Wall: Isolation, Identification and Cytotoxicity against Cancer Cells
Int. J. Mol. Sci. 2014, 15(6), 11111-11125; https://doi.org/10.3390/ijms150611111
Received: 10 April 2014 / Revised: 1 June 2014 / Accepted: 4 June 2014 / Published: 20 June 2014
Cited by 3 | PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
Five new (48) and three known (13) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The structures of all compounds were elucidated through spectroscopic analysis including 2D-NMR and HR-MS. The
[...] Read more.
Five new (48) and three known (13) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The structures of all compounds were elucidated through spectroscopic analysis including 2D-NMR and HR-MS. The absolute configuration of these compounds was established by X-ray diffraction analysis, comparison of NOESY spectra and biogenetic means. The cytotoxities of compounds 28 were evaluated in vitro against HL-60, SMMC-7721, A549, MCF-7 and SW480 cell lines. Compounds 57 exhibited the highest activities with IC50 values of 11.8–30.1 μM in most cases. The SAR revealed that the introduction of hydroxyl group was able to significantly improve the activities of the compounds for most of the cell lines. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessReview Coactivator Recruitment of AhR/ARNT1
Int. J. Mol. Sci. 2014, 15(6), 11100-11110; https://doi.org/10.3390/ijms150611100
Received: 16 April 2014 / Revised: 27 May 2014 / Accepted: 7 June 2014 / Published: 19 June 2014
Cited by 7 | PDF Full-text (1081 KB) | HTML Full-text | XML Full-text
Abstract
A common feature of nuclear receptors (NRs) is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of
[...] Read more.
A common feature of nuclear receptors (NRs) is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of the specific genes in the nucleus. Another common feature of NRs is their dependence on coactivators, which bridge the basic transcriptional machinery and other cofactors to the target genes, in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase (HAT) function. In this review, we focus on our recent findings related to the recruitment of steroid receptor coactivator 1 (SRC1/NCoA1) by the estrogen receptor-α (ERα) and by the arylhydrocarbon receptor/arylhydrocarbon receptor nuclear translocator 1 (AhR/ARNT1) complex. We also describe the extension of our previously published findings regarding the binding between ARNT1.1 exon16 and SRC1e exon 21, via in silico analyses of androgen receptor (AR) NH2-carboxyl-terminal interactions, the results of which were verified by in vitro experiments. Based on these data, we suggest a newly derived tentative binding site of nuclear coactivator 2/glucocorticoid receptor interacting protein-1/transcriptional intermediary factor 2 (NCOA-2/ GRIP-1/TIF-2) for ARNT1.1 exon 16. Furthermore, results obtained by immunoprecipitation have revealed a second leucine-rich binding site for hARNT1.1 exon 16 in SRC1e exon 21 (LSSTDLL). Finally, we discuss the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an endocrine disruptor for estrogen related transcription. Full article
(This article belongs to the Special Issue Mechanisms of Toxicity of Dioxins and Related Compounds)
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Open AccessArticle The Structure and Dynamics of BmR1 Protein from Brugia malayi: In Silico Approaches
Int. J. Mol. Sci. 2014, 15(6), 11082-11099; https://doi.org/10.3390/ijms150611082
Received: 28 January 2014 / Revised: 25 March 2014 / Accepted: 4 June 2014 / Published: 19 June 2014
Cited by 3 | PDF Full-text (1772 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for
[...] Read more.
Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for elimination by year 2020. Therefore, accurate filariasis diagnosis is important for management and elimination programs. A recombinant antigen (BmR1) from the Bm17DIII gene product was used for antibody-based filariasis diagnosis in “Brugia Rapid”. However, the structure and dynamics of BmR1 protein is yet to be elucidated. Here we study the three dimensional structure and dynamics of BmR1 protein using comparative modeling, threading and ab initio protein structure prediction. The best predicted structure obtained via an ab initio method (Rosetta) was further refined and minimized. A total of 5 ns molecular dynamics simulation were performed to investigate the packing of the protein. Here we also identified three epitopes as potential antibody binding sites from the molecular dynamics average structure. The structure and epitopes obtained from this study can be used to design a binder specific against BmR1, thus aiding future development of antigen-based filariasis diagnostics to complement the current diagnostics. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle Does Prop-2-ynylideneamine, HC≡CCH=NH, Exist in Space? A Theoretical and Computational Investigation
Int. J. Mol. Sci. 2014, 15(6), 11064-11081; https://doi.org/10.3390/ijms150611064
Received: 25 March 2014 / Revised: 6 May 2014 / Accepted: 12 May 2014 / Published: 19 June 2014
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Abstract
MP2, DFT and CCSD methods with 6-311++G** and aug-cc-pvdz basis sets have been used to probe the structural changes and relative energies of E-prop-2-ynylideneamine (I), Z-prop-2-ynylideneamine (II), prop-1,2-diene-1-imine (III) and vinyl cyanide (IV). The energy near-equivalence and provenance of preference of isomers and
[...] Read more.
MP2, DFT and CCSD methods with 6-311++G** and aug-cc-pvdz basis sets have been used to probe the structural changes and relative energies of E-prop-2-ynylideneamine (I), Z-prop-2-ynylideneamine (II), prop-1,2-diene-1-imine (III) and vinyl cyanide (IV). The energy near-equivalence and provenance of preference of isomers and tautomers were investigated by NBO calculations using HF and B3LYP methods with 6-311++G** and aug-cc-pvdz basis sets. All substrates have Cs symmetry. The optimized geometries were found to be mainly theoretical method dependent. All elected levels of theory have computed I/II total energy of isomerization (ΔE) of 1.707 to 3.707 kJ/mol in favour of II at 298.15 K. MP2 and CCSD methods have indicated clearly the preference of II over III; while the B3LYP functional predicted nearly similar total energies. All tested levels of theory yielded a global II/IV tautomerization total energy (ΔE) of 137.3–148.4 kJ/mol in support of IV at 298.15 K. The negative values of ΔS indicated that IV is favoured at low temperature. At high temperature, a reverse tautomerization becomes spontaneous and II is preferred. The existence of II in space was debated through the interpretation and analysis of the thermodynamic and kinetic studies of this tautomerization reaction and the presence of similar compounds in the Interstellar Medium (ISM). Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle A Single Nucleotide Polymorphism in the Stromal Cell-Derived Factor 1 Gene Is Associated with Coronary Heart Disease in Chinese Patients
Int. J. Mol. Sci. 2014, 15(6), 11054-11063; https://doi.org/10.3390/ijms150611054
Received: 26 May 2014 / Revised: 6 June 2014 / Accepted: 13 June 2014 / Published: 19 June 2014
Cited by 11 | PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
Coronary heart disease (CHD) is highly prevalent globally and a major cause of mortality. Genetic predisposition is a non-modifiable risk factor associated with CHD. Eighty-four Chinese patients with CHD and 253 healthy Chinese controls without CHD were recruited. Major clinical data were collected,
[...] Read more.
Coronary heart disease (CHD) is highly prevalent globally and a major cause of mortality. Genetic predisposition is a non-modifiable risk factor associated with CHD. Eighty-four Chinese patients with CHD and 253 healthy Chinese controls without CHD were recruited. Major clinical data were collected, and a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene at position 801 (G to A, rs1801157) in the 3'-untranslated region was identified. The correlation between rs1801157 genotypes and CHD was evaluated by a multivariate logistic regression analysis. The allele frequency in the CHD and control groups was in Hardy-Weinberg equilibrium (HWE) (p > 0.05). The frequency of the GG genotype in the CHD group (59.5%) was significantly higher than that in the control group (49.8%) (p = 0.036). A number of variables, including male sex, age, presence of hypertension, and the levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), uric acid, and total bilirubin, were associated with CHD in a primary univariate analysis. In a multivariable logistic regression analysis, the GG genotype (GG:AA, odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.21–5.23), male sex, advanced age (≥60 years), presence of hypertension, LDL-C level ≥ 3.33 mg/dL, HDL-C level < 1.03 mg/dL, and TG level ≥ 1.7 mg/dL were independent risk factors for CHD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle Cellulose Nanocrystals/ZnO as a Bifunctional Reinforcing Nanocomposite for Poly(vinyl alcohol)/Chitosan Blend Films: Fabrication, Characterization and Properties
Int. J. Mol. Sci. 2014, 15(6), 11040-11053; https://doi.org/10.3390/ijms150611040
Received: 4 April 2014 / Revised: 14 May 2014 / Accepted: 26 May 2014 / Published: 18 June 2014
Cited by 19 | PDF Full-text (689 KB) | HTML Full-text | XML Full-text
Abstract
In this study, cellulose nanocrystals/zinc oxide (CNCs/ZnO) nanocomposites were dispersed as bifunctional nano-sized fillers into poly(vinyl alcohol) (PVA) and chitosan (Cs) blend by a solvent casting method to prepare PVA/Cs/CNCs/ZnO bio-nanocomposites films. The morphology, thermal, mechanical and UV-vis absorption properties, as well antimicrobial
[...] Read more.
In this study, cellulose nanocrystals/zinc oxide (CNCs/ZnO) nanocomposites were dispersed as bifunctional nano-sized fillers into poly(vinyl alcohol) (PVA) and chitosan (Cs) blend by a solvent casting method to prepare PVA/Cs/CNCs/ZnO bio-nanocomposites films. The morphology, thermal, mechanical and UV-vis absorption properties, as well antimicrobial effects of the bio-nanocomposite films were investigated. It demonstrated that CNCs/ZnO were compatible with PVA/Cs and dispersed homogeneously in the polymer blend matrix. CNCs/ZnO improved tensile strength and modulus of PVA/Cs significantly. Tensile strength and modulus of bio-nanocomposite films increased from 55.0 to 153.2 MPa and from 395 to 932 MPa, respectively with increasing nano-sized filler amount from 0 to 5.0 wt %. The thermal stability of PVA/Cs was also enhanced at 1.0 wt % CNCs/ZnO loading. UV light can be efficiently absorbed by incorporating ZnO nanoparticles into a PVA/Cs matrix, signifying that these bio-nanocomposite films show good UV-shielding effects. Moreover, the biocomposites films showed antibacterial activity toward the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The improved physical properties obtained by incorporating CNCs/ZnO can be useful in variety uses. Full article
(This article belongs to the Special Issue Biodegradable Materials)
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Open AccessReview Contribution of Chitinase A’s C-Terminal Vacuolar Sorting Determinant to the Study of Soluble Protein Compartmentation
Int. J. Mol. Sci. 2014, 15(6), 11030-11039; https://doi.org/10.3390/ijms150611030
Received: 28 March 2014 / Revised: 6 June 2014 / Accepted: 9 June 2014 / Published: 18 June 2014
Cited by 5 | PDF Full-text (890 KB) | HTML Full-text | XML Full-text
Abstract
Plant chitinases have been studied for their importance in the defense of crop plants from pathogen attacks and for their peculiar vacuolar sorting determinants. A peculiarity of the sequence of many family 19 chitinases is the presence of a C-terminal extension that
[...] Read more.
Plant chitinases have been studied for their importance in the defense of crop plants from pathogen attacks and for their peculiar vacuolar sorting determinants. A peculiarity of the sequence of many family 19 chitinases is the presence of a C-terminal extension that seems to be important for their correct recognition by the vacuole sorting machinery. The 7 amino acids long C-terminal vacuolar sorting determinant (CtVSD) of tobacco chitinase A is necessary and sufficient for the transport to the vacuole. This VSD shares no homology with other CtVSDs such as the phaseolin’s tetrapeptide AFVY (AlaPheValTyr) and it is also sorted by different mechanisms. While a receptor for this signal has not yet been convincingly identified, the research using the chitinase CtVSD has been very informative, leading to the observation of phenomena otherwise difficult to observe such as the presence of separate vacuoles in differentiating cells and the existence of a Golgi-independent route to the vacuole. Thanks to these new insights in the endoplasmic reticulum (ER)-to-vacuole transport, GFPChi (Green Fluorescent Protein carrying the chitinase A CtVSD) and other markers based on chitinase signals will continue to help the investigation of vacuolar biogenesis in plants. Full article
(This article belongs to the Special Issue Plant Cell Compartmentation and Volume Control)
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Open AccessArticle Celecoxib Suppresses the Phosphorylation of STAT3 Protein and Can Enhance the Radiosensitivity of Medulloblastoma-Derived Cancer Stem-Like Cells
Int. J. Mol. Sci. 2014, 15(6), 11013-11029; https://doi.org/10.3390/ijms150611013
Received: 17 March 2014 / Revised: 27 May 2014 / Accepted: 12 June 2014 / Published: 18 June 2014
Cited by 14 | PDF Full-text (4407 KB) | HTML Full-text | XML Full-text
Abstract
Medulloblastoma (MB) is a malignant primary brain tumor with poor prognosis. MB-derived CD133/Nestin double-positive cells (MB-DPs) exhibit cancer stem-like cell (CSC)-like properties that may contribute to chemoradioresistance, tumorigenesis and recurrence. In various tumors, signal transducer and activator of transcription 3 (STAT3) upregulation including
[...] Read more.
Medulloblastoma (MB) is a malignant primary brain tumor with poor prognosis. MB-derived CD133/Nestin double-positive cells (MB-DPs) exhibit cancer stem-like cell (CSC)-like properties that may contribute to chemoradioresistance, tumorigenesis and recurrence. In various tumors, signal transducer and activator of transcription 3 (STAT3) upregulation including MB which can regulate the expression of Nestin. Celecoxib, a selective COX-2 inhibitor, has been shown to potentially reduce STAT3 phosphorylation. The aim of the present study was to investigate the role of celecoxib in enhancing the effects of ionizing radiotherapy (IR) on MB-DP. MB-DPs and MB-derived CD133/Nestin double-negative cells (MB-DNs) were isolated from medulloblastoma cell line Daoy. Then, both of them were treated with celecoxib in different concentrations, and cell viability was assessed. The assays of cell survival, sphere formation, radiosensitivity, colony formation, apoptotic activity and mouse xenografting experiments in MB-DPs and MB-DNs treated with celecoxib alone, radiation alone, or celecoxib combined with radiation were further evaluated. We isolated MB-DPs from MB cell line Daoy, which exhibited typical CSC-like characteristics. Microarray analysis and Western blotting both indicated the upregulation of Janus kinase (JAK)-STAT cascade and STAT3 phosphorylation. Incubation with celecoxib dose-dependently suppressed the CSC-like properties and enhanced the IR effect on the induction of apoptosis, as detected by TUNEL assay and staining for Caspase 3 and Annexin V. Finally, celecoxib also enhanced the IR effect to suppress tumorigenesis and synergistically improve the recipient survival in orthotopic MB-derived CD133/Nestin double-positive cells (MB-DP cells) bearing mice. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle The Effects of CoCl2 on HIF-1α Protein under Experimental Conditions of Autoprogressive Hypoxia Using Mouse Models
Int. J. Mol. Sci. 2014, 15(6), 10999-11012; https://doi.org/10.3390/ijms150610999
Received: 28 February 2014 / Revised: 10 June 2014 / Accepted: 11 June 2014 / Published: 18 June 2014
Cited by 12 | PDF Full-text (949 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
It is well known that cobalt chloride (CoCl2) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive
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It is well known that cobalt chloride (CoCl2) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl2 and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl2 group. Over-induction of HIF-1α by pretreatment with CoCl2 before hypoxia did not increase the hypoxia tolerance. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle Correlation between BPI Gene Upstream CpG Island Methylation and mRNA Expression in Piglets
Int. J. Mol. Sci. 2014, 15(6), 10989-10998; https://doi.org/10.3390/ijms150610989
Received: 12 May 2014 / Revised: 28 May 2014 / Accepted: 9 June 2014 / Published: 18 June 2014
Cited by 2 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Diarrhea and edematous disease are two major causes of mortality in postweaning piglets, and these conditions lead to huge economic losses in the swine industry. E. coli F18 is the primary causative agent of these two diseases. Bactericidal/permeability-increasing protein (BPI) plays an important
[...] Read more.
Diarrhea and edematous disease are two major causes of mortality in postweaning piglets, and these conditions lead to huge economic losses in the swine industry. E. coli F18 is the primary causative agent of these two diseases. Bactericidal/permeability-increasing protein (BPI) plays an important role in the natural defense of the host. The aim of this study was to determine the correlation between BPI gene upstream CpG island methylation and mRNA expression. In this study, bisulfite sequencing PCR (BSP) was used to detect the methylation status of the BPI gene upstream CpG island and fluorescence quantitative PCR was used to detect BPI expression in the duodenum of piglets from birth to weaning age. BPI upstream CpG islands were shown to have many putative transcription factor binding sites, 10 CpG sites and every CpG site was methylated. The CpG island methylation level was lowest in 30-day piglets and was significantly lower than levels in 8-day piglets (p < 0.05). BPI mRNA expression was significantly higher in 30-day piglets than at any other age (p < 0.05). Pearson’s correlation analysis showed that the methylation status of the CpG island was negatively correlated with BPI mRNA expression. Statistical significances were found in CpG_1, CpG_3, CpG_4, CpG_7 and CpG_10 (p < 0.05). The data indicate that BPI expression is improved by demethylation of the BPI gene upstream CpG island. Furthermore, CpG_1, CpG_3, CpG_4, CpG_7 and CpG_10 may be critical sites in the regulation of BPI gene expression. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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