World Journal Of Biological Chemistry[JOURNAL]
Sun
200 papers
Adaptive and maladaptive expression of the mRNA regulatory protein HuR.
Govindaraju S, Lee BS
World J Biol Chem · 2013 Nov · PMID 24340134 · Full text
The RNA-binding proteins involved in regulation of mRNA post-transcriptional processing and translation control the fates of thousands of mRNA transcripts and basic cellular processes. The best studied of these, HuR, is...
The RNA-binding proteins involved in regulation of mRNA post-transcriptional processing and translation control the fates of thousands of mRNA transcripts and basic cellular processes. The best studied of these, HuR, is well characterized as a mediator of mRNA stability and translation, and more recently, as a factor in nuclear functions such as pre-mRNA splicing. Due to HuR's role in regulating thousands of mRNA transcripts, including those for other RNA-binding proteins, HuR can act as a master regulator of cell survival and proliferation. HuR itself is subject to multiple post-translational modifications including regulation of its nucleocytoplasmic distribution. However, the mechanisms that govern HuR levels in the cell have only recently begun to be defined. These mechanisms are critical to cell health, as it has become clear in recent years that aberrant expression of HuR can lead alternately to decreased cell viability or to promotion of pathological proliferation and invasiveness. HuR is expressed as alternate mRNAs that vary in their untranslated regions, leading to differences in transcript stability and translatability. Multiple transcription factors and modulators of mRNA stability that regulate HuR mRNA expression have been identified. In addition, translation of HuR is regulated by numerous microRNAs, several of which have been demonstrated to have anti-tumor properties due to their suppression of HuR expression. This review summarizes the current state of knowledge of the factors that regulate HuR expression, along with the circumstances under which these factors contribute to cancer and inflammation.
Lipidomic mass spectrometry and its application in neuroscience.
Enriquez-Algeciras M, Bhattacharya SK
World J Biol Chem · 2013 Nov · PMID 24340133 · Full text
Central and peripheral nervous systems are lipid rich tissues. Lipids, in the context of lipid-protein complexes, surround neurons and provide electrical insulation for transmission of signals allowing neurons to remain...
Central and peripheral nervous systems are lipid rich tissues. Lipids, in the context of lipid-protein complexes, surround neurons and provide electrical insulation for transmission of signals allowing neurons to remain embedded within a conducting environment. Lipids play a key role in vesicle formation and fusion in synapses. They provide means of rapid signaling, cell motility and migration for astrocytes and other cell types that surround and play supporting roles neurons. Unlike many other signaling molecules, lipids are capable of multiple signaling events based on the different fragments generated from a single precursor during each event. Lipidomics, until recently suffered from two major disadvantages: (1) level of expertise required an overwhelming amount of chemical detail to correctly identify a vast number of different lipids which could be close in their chemical reactivity; and (2) high amount of purified compounds needed by analytical techniques to determine their structures. Advances in mass spectrometry have enabled overcoming these two limitations. Mass spectrometry offers a great degree of simplicity in identification and quantification of lipids directly extracted from complex biological mixtures. Mass spectrometers can be regarded to as mass analyzers. There are those that separate and analyze the product ion fragments in space (spatial) and those which separate product ions in time in the same space (temporal). Databases and standardized instrument parameters have further aided the capabilities of the spatial instruments while recent advances in bioinformatics have made the identification and quantification possible using temporal instruments.
Cathepsins mediate tumor metastasis.
Tan GJ, Peng ZK, Lu JP … +1 more , Tang FQ
World J Biol Chem · 2013 Nov · PMID 24340132 · Full text
Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases o...
Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.
Rethinking quasispecies theory: From fittest type to cooperative consortia.
Villarreal LP, Witzany G
World J Biol Chem · 2013 Nov · PMID 24340131 · Full text
Recent investigations surprisingly indicate that single RNA "stem-loops" operate solely by chemical laws that act without selective forces, and in contrast, self-ligated consortia of RNA stem-loops operate by biological...
Recent investigations surprisingly indicate that single RNA "stem-loops" operate solely by chemical laws that act without selective forces, and in contrast, self-ligated consortia of RNA stem-loops operate by biological selection. To understand consortial RNA selection, the concept of single quasi-species and its mutant spectra as drivers of RNA variation and evolution is rethought here. Instead, we evaluate the current RNA world scenario in which consortia of cooperating RNA stem-loops (not individuals) are the basic players. We thus redefine quasispecies as RNA quasispecies consortia (qs-c) and argue that it has essential behavioral motifs that are relevant to the inherent variation, evolution and diversity in biology. We propose that qs-c is an especially innovative force. We apply qs-c thinking to RNA stem-loops and evaluate how it yields altered bulges and loops in the stem-loop regions, not as errors, but as a natural capability to generate diversity. This basic competence-not error-opens a variety of combinatorial possibilities which may alter and create new biological interactions, identities and newly emerged self identity (immunity) functions. Thus RNA stem-loops typically operate as cooperative modules, like members of social groups. From such qs-c of stem-loop groups we can trace a variety of RNA secondary structures such as ribozymes, viroids, viruses, mobile genetic elements as abundant infection derived agents that provide the stem-loop societies of small and long non-coding RNAs.
Potent trophic activity of spermidine supramolecular complexes in in vitro models.
Ghisalberti CA, Morisetti A, Bestetti A … +1 more , Cairo G
World J Biol Chem · 2013 Aug · PMID 23977423 · Full text
AIM: To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes. METHODS: A thiazolyl blue cell viability assay was used to determine the growth-pro...
AIM: To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes. METHODS: A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin. Reconstituted human vaginal epithelium was exposed to a specific spermidine-supramolecular complex, i.e., spermidine-hyaluronan (HA) 50, and cell proliferation was determined by Ki-67 immunohistochemical detection. Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity. RESULTS: The effect of spermidine and spermidine-supramolecular complexes was first tested in skin fibroblasts. Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition, whereas 30% stimulation over basal levels was detected at μmol/L and nmol/L levels. Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers, such as HA, alginate, and polymaleate, were then tested at variable spermidine concentrations and a fixed polymer level (0.1% w/v). Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency (up to 80%) at sub-μmol/L levels. Similar results were obtained with spermidine-(α-cyclodextrin), another type of spermidine-supramolecular complex. Moreover, the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation. Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA, thus supporting its safety. CONCLUSION: Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects. Safety data on reconstituted human vaginal epithelium suggested that assessing spermidine-supramolecular complex efficacy in atrophic disorders is justified.
Autophagy and cancer.
Lu SZ, Harrison-Findik DD
World J Biol Chem · 2013 Aug · PMID 23977422 · Full text
Autophagy is a homeostatic and evolutionarily conserved mechanism of self-digestion by which the cells degrade and recycle long-lived proteins and excess or damaged organelles. Autophagy is activated in response to both...
Autophagy is a homeostatic and evolutionarily conserved mechanism of self-digestion by which the cells degrade and recycle long-lived proteins and excess or damaged organelles. Autophagy is activated in response to both physiological and pathological stimuli including growth factor depletion, energy deficiency or the upregulation of Bcl-2 protein expression. A novel role of autophagy in various cancers has been proposed. Interestingly, evidence that supports both a positive and negative role of autophagy in the pathogenesis of cancer has been reported. As a tumor suppression mechanism, autophagy maintains genome stability, induces senescence and possibly autophagic cell death. On the other hand, autophagy participates in tumor growth and maintenance by supplying metabolic substrate, limiting oxidative stress, and maintaining cancer stem cell population. It has been proposed that the differential roles of autophagy in cancer are disease type and stage specific. In addition, substrate selectivity might be involved in carrying out the specific effect of autophagy in cancer, and represents one of the potential directions for future studies.
Molecular recognition by gold, silver and copper nanoparticles.
Tauran Y, Brioude A, Coleman AW … +2 more , Rhimi M, Kim B
World J Biol Chem · 2013 Aug · PMID 23977421 · Full text
The intrinsic physical properties of the noble metal nanoparticles, which are highly sensitive to the nature of their local molecular environment, make such systems ideal for the detection of molecular recognition events...
The intrinsic physical properties of the noble metal nanoparticles, which are highly sensitive to the nature of their local molecular environment, make such systems ideal for the detection of molecular recognition events. The current review describes the state of the art concerning molecular recognition of Noble metal nanoparticles. In the first part the preparation of such nanoparticles is discussed along with methods of capping and stabilization. A brief discussion of the three common methods of functionalization: Electrostatic adsorption; Chemisorption; Affinity-based coordination is given. In the second section a discussion of the optical and electrical properties of nanoparticles is given to aid the reader in understanding the use of such properties in molecular recognition. In the main section the various types of capping agents for molecular recognition; nucleic acid coatings, protein coatings and molecules from the family of supramolecular chemistry are described along with their numerous applications. Emphasis for the nucleic acids is on complementary oligonucleotide and aptamer recognition. For the proteins the recognition properties of antibodies form the core of the section. With respect to the supramolecular systems the cyclodextrins, calix[n]arenes, dendrimers, crown ethers and the cucurbitales are treated in depth. Finally a short section deals with the possible toxicity of the nanoparticles, a concern in public health.
Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes.
Galliher-Beckley AJ, Lan LQ, Aono S … +2 more , Wang L, Shi J
World J Biol Chem · 2013 May · PMID 23710297 · Full text
AIM: To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β (pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events. METHODS: All experiment...
AIM: To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β (pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events. METHODS: All experiments were performed on fresh or overnight cultured human peripheral blood monocytes (PBMCs) that were isolated from healthy donors. PBMCs were activated by lipopolysaccharide (LPS) stimulation before being treated with Adenosine triphosphate (ATP, 1 mmol/L), human α-defensin-5 (HD-5, 50 μg/mL), and/or nigericin (Nig, 30 μmol/L). For each experiment, the culture supernatants were collected separately from the cells. Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL-1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies. RESULTS: We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation. In the presence of HD-5, this release of IL-1β, but not the processing of pro-IL-1β to IL-1β, was completely inhibited. Similarly, in the presence of HD-5, the release of IL-1β, but not the processing of IL-1β, was significantly inhibited from LPS-activated monocytes stimulated with Nig. Finally, we treated LPS-activated monocytes with ATP and Nig and collected the supernatants. We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes. Interestingly, and contrary to IL-1β processing and release, caspase-1 cleavage and release was not blocked by HD-5. All images are representative of three independent experiments. CONCLUSION: These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.
Refractoriness of interferon-beta signaling through NOD1 pathway in mouse respiratory epithelial cells using the anticancer xanthone compound.
Yu Z, Predina JD, Cheng G
World J Biol Chem · 2013 May · PMID 23710296 · Full text
AIM: To explore the possibility that nucleotide oligomerization domain 1 (NOD1) pathway involved in refractoriness of interferon-β signaling in mouse respiratory epithelial cells induced by the anticancer xanthone compou...
AIM: To explore the possibility that nucleotide oligomerization domain 1 (NOD1) pathway involved in refractoriness of interferon-β signaling in mouse respiratory epithelial cells induced by the anticancer xanthone compound, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). METHODS: C10 mouse bronchial epithelial cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine, 100 units/mL penicillin, 100 g/mL streptomycin. Pathogen-free female BALB/c mice were used to explore the mechanisms of refractoriness of interferon-signaling. Mouse thioglycollate-elicited peritoneal macrophages, bone marrow derived macrophages and bone marrow derived dendritic cells were collected and cultured. The amount of interferon (IFN)-inducible protein-10 (IP10/CXCL10), macrophage chemotactic protein (MCP1/CCL2) and interleukin (IL)-6 secreted by cells activated by DMXAA was quantified using enzyme-linked immunosorbent assay kits according to the instructions of the manufacturers. Total RNA was isolated from cells or nasal epithelium with RNeasy Plus Mini Kit, and cDNA was synthesized. Gene expression was checked using Applied Biosystems StepOne Real-Time Polymerase Chain Reaction System. Transfection of small interfering RNA (siRNA) control, NOD1 duplexed RNA oligonucleotides, and high-mobility group box 1/2/3 (HMGB1/2/3) siRNA was performed using siRNA transfection reagent. RESULTS: DMXAA activates IFN-β pathway with high level of IFN-β dependent antiviral genes including 2', 5'-oligoadenylate synthetase 1 and myxovirus resistance 1 in mouse thioglycollate-elicited peritoneal macrophages, bone marrow derived macrophages and bone marrow derived dendritic cells. Activation of IFN-β by DMXAA involved in NOD1, but not HMGB1/2/3 signal pathway demonstrated by siRNA. NOD1 pathway plays an important role in refractoriness of IFN-β signaling induced by DMXAA in mouse C10 respiratory epithelial cells and BALB/c mice nasal epithelia. These data indicate that DMXAA is not well adapted to the intrinsic properties of IFN-β signaling. Approaches to restore sensitivity of IFN-β signaling by find other xanthone compounds may function similarly, could enhance the efficacy of protection from influenza pneumonia and potentially in other respiratory viral infections. CONCLUSION: NOD1 pathway may play an important role in refractoriness of IFN-β signaling in mouse respiratory epithelial cells induced by DMXAA.
Heart and Brain: A neutro-genomic link.
Dave VP, Kaul D
World J Biol Chem · 2013 May · PMID 23710295 · Full text
The philosophy of heart and brain are very ancient in our literature where the things good for the heart are not suggested good for the brain and vice-versa. Modern medicine is characterized by a high degree of specializ...
The philosophy of heart and brain are very ancient in our literature where the things good for the heart are not suggested good for the brain and vice-versa. Modern medicine is characterized by a high degree of specialization and the heart-brain connection that could be targeted to treat these complex cardiovascular/brain disorders. The idea that adverse diet/genome interactions can cause disease is not new. In the recent era the science of nutritional genomics have increased our understanding of diet-health-gene interactions and have provided a number of benefits for individuals, groups and societies. Since dietary chemicals are regularly ingested and participate indirectly and directly in regulating gene expression, it follows that a subset of genes regulated by diet must be involved in disease initiation, progression, and severity. In this regards Liver X Receptor (LXR)-α, a key transcription factors, associated with the several chronic pathological situation including coronary heart disease and neurodegenerative diseases have recently been found to be regulated by the dietary components. The crucial findings at molecular biology unit, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, INDIA have not only forced us to explore nutritional genomics as a holistic systems approach to understand the relationship between diet and health, but also to look into the disease preventing and health promoting foods that match our lifestyles, cultures and genetics. After all, we are what we eat.
At the dawn of a new revolution in life sciences.
Baluška F, Witzany G
World J Biol Chem · 2013 May · PMID 23710294 · Full text
In a recently published article Sydney Brenner argued that the most relevant scientific revolution in biology at his time was the breakthrough of the role of "information" in biology. The fundamental concept that integra...
In a recently published article Sydney Brenner argued that the most relevant scientific revolution in biology at his time was the breakthrough of the role of "information" in biology. The fundamental concept that integrates this new biological "information" with matter and energy is the universal Turing machine and von Neumann's self-reproducing machines. In this article we demonstrate that in contrast to Turing/von Neumann machines living cells can really reproduce themselves. Additionally current knowledge on the roles of non-coding RNAs indicates a radical violation of the central dogma of molecular biology and opens the way to a new revolution in life sciences.
S100B protein in tissue development, repair and regeneration.
Sorci G, Riuzzi F, Arcuri C … +4 more , Tubaro C, Bianchi R, Giambanco I, Donato R
World J Biol Chem · 2013 Feb · PMID 23580916 · Full text
The Ca(2+)-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcrip...
The Ca(2+)-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcription, protein phosphorylation, cell proliferation, survival, differentiation and motility, and Ca(2+) homeostasis, by interacting with a wide array of proteins (i.e., enzymes, enzyme substrates, cytoskeletal subunits, scaffold/adaptor proteins, transcription factors, ubiquitin E3 ligases, ion channels) in a restricted number of cell types. As an extracellular signal, S100B engages the pattern recognition receptor, receptor for advanced glycation end-products (RAGE), on immune cells as well as on neuronal, astrocytic and microglial cells, vascular smooth muscle cells, skeletal myoblasts and cardiomyocytes. However, RAGE may not be the sole receptor activated by S100B, the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types. Moreover, extracellular effects of S100B vary depending on its local concentration. Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury, which is up to a few nM levels, S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis. The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development, repair and regeneration.
Frontier of therapeutic antibody discovery: The challenges and how to face them.
Lu ZJ, Deng SJ, Huang DG … +4 more , He Y, Lei M, Zhou L, Jin P
World J Biol Chem · 2012 Dec · PMID 23275803 · Full text
Therapeutic monoclonal antibodies have become an important class of modern medicines. The established technologies for therapeutic antibody discovery such as humanization of mouse antibodies, phage display of human antib...
Therapeutic monoclonal antibodies have become an important class of modern medicines. The established technologies for therapeutic antibody discovery such as humanization of mouse antibodies, phage display of human antibody libraries and transgenic animals harboring human IgG genes have been practiced successfully so far, and many incremental improvements are being made constantly. These methodologies are responsible for currently marketed therapeutic antibodies and for the biopharma industry pipeline which are concentrated on only a few dozen targets. A key challenge for wider application of biotherapeutic approaches is the paucity of truly validated targets for biotherapeutic intervention. The efforts to expand the target space include taking the pathway approach to study the disease correlation. Since many new targets are multi-spanning and multimeric membrane proteins there is a need to develop more effective methods to generate antibodies against these difficult targets. The pharmaceutical properties of therapeutic antibodies are an active area for study concentrating on biophysical characteristics such as thermal stability and aggregation propensity. The immunogenicity of biotherapeutics in humans is a very complex issue and there are no truly predictive animal models to rely on. The in silico and T-cell response approaches identify the potential for immunogenicity; however, one needs contingency plans for emergence of anti-product antibody response for clinical trials.
Transglutaminase inhibition: A therapy to protect cells from death in neurodegeneration?
Iannaccone M, Stefanile A, Vivo GD … +3 more , Martin A, Serretiello E, Gentile V
World J Biol Chem · 2012 Nov · PMID 23193435 · Full text
Transglutaminases (TGs; E.C. 2.3.2.13) are ubiquitous enzymes which catalyze post-translational modifications of proteins. TGs and TG-catalyzed post-translational modifications of proteins have been shown to be involved...
Transglutaminases (TGs; E.C. 2.3.2.13) are ubiquitous enzymes which catalyze post-translational modifications of proteins. TGs and TG-catalyzed post-translational modifications of proteins have been shown to be involved in the molecular mechanisms responsible for several human diseases. In particular, TG activity has been hypothesized to also be involved also in the molecular mechanisms responsible for human neurodegenerative diseases. In support of this hypothesis, Basso et al recently demonstrated that the TG inhibition protects against oxidative stress-induced neuronal death, suggesting that multiple TG isoforms participate in oxidative stress-induced cell death and that nonselective TG isoform inhibitors will be most effective in fighting oxidative death in neurological disorders. In this commentary, we discuss the possible molecular mechanisms by which TG activity could be involved in the pathogenesis of neurological diseases, with particular reference to neurodegenerative diseases, and the possible involvement of multiple TG isoforms expressed simultaneously in the nervous system in these diseases. Moreover, therapeutic strategies based on the use of selective or nonselective TG inhibitors for the amelioration of the symptoms of patients with neurological diseases, characterized by aberrant TG activity, are also discussed.
Salivary immunoglobulin classes in Nigerian smokers with periodontitis.
Olayanju OA, Rahamon SK, Joseph IO … +1 more , Arinola OG
World J Biol Chem · 2012 Oct · PMID 23115655 · Full text
AIM: To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis. METHODS: Sixty-nine individuals were recruited into this study after obtaining informed consent. The...
AIM: To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis. METHODS: Sixty-nine individuals were recruited into this study after obtaining informed consent. They were subdivided into three groups that consisted of 20 (aged 46 ± 11 years) cigarette smokers with periodontitis (S+P); 24 (40 ± 12 years) smokers without periodontitis (S-P); and 25 (53 ± 11 years) non-smokers with periodontitis (NS+P). An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis. The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed. About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles. Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay. Student's t test was used to determine significant differences between the means. Values of P < 0.05 were regarded as significant. RESULTS: No significant differences were observed in the mean salivary levels of the immunoglobulin classes (IgG, IgA, IgM and IgE) when S+P was compared with S-P. Mean salivary levels of IgA (520.0 ± 155.1 ng/mL vs 670.0 ± 110 ng/mL, P = 0.000) and IgM (644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.000) were significantly lower in the S+P compared with NS+P group. Salivary IgA (570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL, P = 0.008) and IgM (703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.012) levels were significantly lower in the S-P compared with NS+P group. Only one (5%) periodontal patient had detectable levels of salivary IgE (0.20 IU/mL). Similarly, only one smoker (4.17%) had detectable levels of salivary IgE (0.04 IU/mL) and two non-smokers (9.52%) had detectable levels of IgE (0.24 IU/mL). CONCLUSION: Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.
Nuclear accumulation of β-catenin and forkhead box O3a in colon cancer: Dangerous liaison.
Link W
World J Biol Chem · 2012 Sep · PMID 23024836 · Full text
The WNT/β-catenin and phosphoinositide 3-kinase (PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer. Oncogenic PI3K/AKT signaling suppresses the activity of forkh...
The WNT/β-catenin and phosphoinositide 3-kinase (PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer. Oncogenic PI3K/AKT signaling suppresses the activity of forkhead box O3a (FOXO3a) transcription factor through phosphorylation leading to its nuclear exclusion. Inhibition of the PI3K/AKT signaling by PI3K or AKT inhibitors results in the translocation of FOXO3a to the nucleus, and is considered to be a promising therapeutic strategy for many cancers including colon cancer. Now, however, a new study in Nature Medicine has revealed a nuclear interaction of β-catenin with FOXO3a as a promoter of metastatic progression in colon cancer. The work has important implications for the treatment of colon cancers, suggests a companion biomarker strategy to enable a personalized medicine approach, and offers an alternative therapeutic strategy to overcome resistance to PI3K and AKT inhibitors.
Dysregulated lipid metabolism in cancer.
Zhang F, Du G
World J Biol Chem · 2012 Aug · PMID 22937213 · Full text
Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic sign...
Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.
Lipopolysaccharide triggers nuclear import of Lpcat1 to regulate inducible gene expression in lung epithelia.
Ellis B, Kaercher L, Snavely C … +2 more , Zhao Y, Zou C
World J Biol Chem · 2012 Jul · PMID 22905292 · Full text
AIM: To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene transcription. METHODS: Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus in...
AIM: To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene transcription. METHODS: Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus influenza and Escherichia coli infection was analyzed by employing quantitative Reverse Transcription Polymerase Chain Reaction techniques. Nucleofection was used to deliver Lenti-viral system to express or knock down Lpcat1 in MLE cells. Subcellular protein fractionation and Western blotting were utilized to study Lpcat1 nuclear relocation. RESULTS: Lpcat1 translocates into the nucleus from the cytoplasm in murine lung epithelia (MLE) after LPS treatment. Haemophilus influenza and Escherichia coli, two LPS-containing pathogens that cause pneumonia, triggered Lpcat1 nuclear translocation from the cytoplasm. The LPS inducible gene expression profile was determined by quantitative reverse transcription polymerase chain reaction after silencing Lpcat1 or overexpression of the enzyme in MLE cells. We detected that 17 out of a total 38 screened genes were upregulated, 14 genes were suppressed, and 7 genes remained unchanged in LPS treated cells in comparison to controls. Knockdown of Lpcat1 by shRNA dramatically changed the spectrum of the LPS inducible gene transcription, as 18 genes out of 38 genes were upregulated, of which 20 genes were suppressed or unchanged. Notably, in Lpcat1 overexpressed cells, 25 genes out of 38 genes were reduced in the setting of LPS treatment. CONCLUSION: These observations suggest that Lpcat1 relocates into the nucleus in response to bacterial infection to differentially regulate gene transcriptional repression.
Update on vascular endothelial Ca(2+) signalling: A tale of ion channels, pumps and transporters.
Moccia F, Berra-Romani R, Tanzi F
World J Biol Chem · 2012 Jul · PMID 22905291 · Full text
A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescenc...
A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca(2+) signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca(2+) levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca(2+) signals, ranging from brief, localized Ca(2+) pulses to prolonged Ca(2+) oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca(2+) signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca(2+) releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca(2+) removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca(2+) machinery in vascular ECs under both physiological and pathological conditions.
Multilevel complexity of calcium signaling: Modeling angiogenesis.
Munaron L, Scianna M
World J Biol Chem · 2012 Jun · PMID 22905290 · Full text
Intracellular calcium signaling is a universal, evolutionary conserved and versatile regulator of cell biochemistry. The complexity of calcium signaling and related cell machinery can be investigated by the use of experi...
Intracellular calcium signaling is a universal, evolutionary conserved and versatile regulator of cell biochemistry. The complexity of calcium signaling and related cell machinery can be investigated by the use of experimental strategies, as well as by computational approaches. Vascular endothelium is a fascinating model to study the specific properties and roles of calcium signals at multiple biological levels. During the past 20 years, live cell imaging, patch clamp and other techniques have allowed us to detect and interfere with calcium signaling in endothelial cells (ECs), providing a huge amount of information on the regulation of vascularization (angiogenesis) in normal and tumoral tissues. These data range from the spatiotemporal dynamics of calcium within different cell microcompartments to those in entire multicellular and organized EC networks. Beside experimental strategies, in silico endothelial models, specifically designed for simulating calcium signaling, are contributing to our knowledge of vascular physiology and pathology. They help to investigate and predict the quantitative features of proangiogenic events moving through subcellular, cellular and supracellular levels. This review focuses on some recent developments of computational approaches for proangiogenic endothelial calcium signaling. In particular, we discuss the creation of hybrid simulation environments, which combine and integrate discrete Cellular Potts Models. They are able to capture the phenomenological mechanisms of cell morphological reorganization, migration, and intercellular adhesion, with single-cell spatiotemporal models, based on reaction-diffusion equations that describe the agonist-induced intracellular calcium events.
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