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Int. J. Mol. Sci., Volume 15, Issue 2 (February 2014), Pages 1686-3355

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Open AccessArticle C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells
Int. J. Mol. Sci. 2014, 15(2), 3336-3355; https://doi.org/10.3390/ijms15023336
Received: 19 November 2013 / Revised: 20 January 2014 / Accepted: 11 February 2014 / Published: 21 February 2014
Cited by 14 | PDF Full-text (1441 KB) | HTML Full-text | XML Full-text
Abstract
Ceramides are second messengers involved in several intracellular processes in cancer cells, amongst others. The aim of this study was to evaluate the anti-tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-D-sphingosine) by investigating cell death and autophagy in head and neck squamous cell carcinoma
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Ceramides are second messengers involved in several intracellular processes in cancer cells, amongst others. The aim of this study was to evaluate the anti-tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-D-sphingosine) by investigating cell death and autophagy in head and neck squamous cell carcinoma (HNSCC) cells. C2-Cer showed concentration-dependent cytotoxicity in HN4 and HN30 cell lines. It simultaneously induced caspase-3-independent apoptosis and programmed necrosis. C2-Cer markedly increased the expression level of microtubule-associated protein 1 light chain 3B (LC3B) type II associated with protective autophagy. An autophagy inhibitor enhanced C2-Cer-mediated cytotoxicity, while a programmed-necrosis inhibitor produced the opposite effect. Furthermore, C2-Cer up-regulated the phosphorylation of extracellular signal-regulated kinase 1/2, but down-regulated its downstream substrate phospho-mammalian target of rapamycin (p-mTOR) during the autophagy process. These results suggested that C2-Cer exerts anti-tumor effects by inducing programmed apoptosis and necrosis in HNSCC, and these cytotoxic effects are enhanced by an autophagy inhibitor. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle The Glutathione Peroxidase Gene Family in Thellungiella salsuginea: Genome-Wide Identification, Classification, and Gene and Protein Expression Analysis under Stress Conditions
Int. J. Mol. Sci. 2014, 15(2), 3319-3335; https://doi.org/10.3390/ijms15023319
Received: 22 January 2014 / Revised: 17 February 2014 / Accepted: 17 February 2014 / Published: 21 February 2014
Cited by 13 | PDF Full-text (1460 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glutathione peroxidases (GPX) catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols using reduced glutathione, which plays an essential role in ROS (reactive oxygen species) homeostasis and stress signaling. Thellungiella salsuginea (Eutrema salsugineum), a
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Glutathione peroxidases (GPX) catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols using reduced glutathione, which plays an essential role in ROS (reactive oxygen species) homeostasis and stress signaling. Thellungiella salsuginea (Eutrema salsugineum), a relative of Arabidopsis thaliana, displays an extremely high level of tolerance to salt, drought, cold and oxidative stresses. The enzymatic antioxidant systems may contribute to the stress tolerance of T. salsuginea. In the present study, we aimed at understanding the roles of the antioxidant enzymes in T. salsuginea by focusing on the GPX family. We identified the eight GPX genes in T. salsuginea, and the structure of the N-terminal domains indicated their putative chloroplastic, mitochondrial and cytoplasmic location. The exon-intron organization of these genes exhibited a conserved pattern among plant GPX genes. Multiple environmental stresses and hormone response related cis-acting elements were predicted in the promoters of TsGPX genes. The gene and protein expression profiles of TsGPXs in response to high level of salinity and osmotic stresses, in leaves and roots of T. salsuginea were investigated using real-time RT-PCR and western blotting analysis. Our result showed that different members of the GPX gene family were coordinately regulated under specific environmental stress conditions, and supported the important roles of TsGPXs in salt and drought stress response in T. salsuginea. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Expression of PHB2 in Rat Brain Cortex Following Traumatic Brain Injury
Int. J. Mol. Sci. 2014, 15(2), 3299-3318; https://doi.org/10.3390/ijms15023299
Received: 13 November 2013 / Revised: 31 January 2014 / Accepted: 13 February 2014 / Published: 21 February 2014
Cited by 6 | PDF Full-text (1898 KB) | HTML Full-text | XML Full-text
Abstract
Prohibitin2 (PHB2) is a ubiquitous, evolutionarily strongly conserved protein. It is one of the components of the prohibitin complex, which comprises two highly homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular compartments including the nucleus and mitochondria. Recent studies have
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Prohibitin2 (PHB2) is a ubiquitous, evolutionarily strongly conserved protein. It is one of the components of the prohibitin complex, which comprises two highly homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular compartments including the nucleus and mitochondria. Recent studies have identified PHB2 as a multifunctional protein that controls cell proliferation, apoptosis, cristae morphogenesis and the functional integrity of mitochondria. However its distribution and function in the central nervous system (CNS) are not well understood. In this study, we examined PHB2 expression and cellular localization in rats after acute traumatic brain injury (TBI). Western Blot analysis showed PHB2 level was significantly enhanced at five days after injury compared to control, and then declined during the following days. The protein expression of PHB2 was further analyzed by immunohistochemistry. In comparison to contralateral cerebral cortex, we observed a highly significant accumulation of PHB2 at the ipsilateral brain. Immunofluorescence double-labeling showed that PHB2 was co-expressed with NeuN, GFAP. Besides, PHB2 also colocalized with activated caspase-3 and PCNA. To further investigate the function of PHB2, primary cultured astrocytes and the neuronal cell line PC12 were employed to establish a proliferation model and an apoptosis model, respectively, to simulate the cell activity after TBI to a certain degree. Knocking down PHB2 by siRNA partly increased the apoptosis level of PC12 stimulated by H2O2. While the PHB2 was interrupted by siRNA, the proliferation level of primary cultured astrocytes was inhibited notably than that in the control group. Together with our data, we hypothesized that PHB2 might play an important role in CNS pathophysiology after TBI. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
Open AccessArticle Novel Microwave-Assisted Synthesis of the Immunomodulator Organotellurium Compound Ammonium Trichloro(dioxoethylene-O,O')tellurate (AS101)
Int. J. Mol. Sci. 2014, 15(2), 3287-3298; https://doi.org/10.3390/ijms15023287
Received: 21 January 2014 / Revised: 11 February 2014 / Accepted: 17 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (487 KB) | HTML Full-text | XML Full-text
Abstract
Ammonium trichloro[1,2-ethanediolato-O,O']-tellurate (AS101) is the most important synthetic Te compound from the standpoint of its biological activity. It is a potent immunomodulator with a variety of potential therapeutic applications and antitumoral action in several preclinical and clinical studies. An
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Ammonium trichloro[1,2-ethanediolato-O,O']-tellurate (AS101) is the most important synthetic Te compound from the standpoint of its biological activity. It is a potent immunomodulator with a variety of potential therapeutic applications and antitumoral action in several preclinical and clinical studies. An experimental design has been used to develop and optimize a novel microwave-assisted synthesis (MAOS) of the AS101. In comparison to the results observed in the literature, refluxing Te(IV) chloride and ethylene glycol in acetonitrile (Method A), or by refluxing Te(IV) chloride and ammonium chloride in ethylene glycol (Method B), it was found that the developed methods in the present work are an effective alternative, because although performance slightly decreases compared to conventional procedures (75% vs. 79% by Method A, and 45% vs. 51% by Method B), reaction times decreased from 4 h to 30 min and from 4 h to 10 min, by Methods A and B respectively. MAOS is proving to be of value in the rapid synthesis of compounds with new and improved biological activities, specially based on the benefit of its shorter reaction times. Full article
(This article belongs to the Section Green Chemistry)
Open AccessArticle Characterization of Bactrocera dorsalis Serine Proteases and Evidence for Their Indirect Role in Insecticide Tolerance
Int. J. Mol. Sci. 2014, 15(2), 3272-3286; https://doi.org/10.3390/ijms15023272
Received: 20 December 2013 / Revised: 9 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text
Abstract
The oriental fruit fly Bactrocera dorsalis (Hendel) causes devastating losses to agricultural crops world-wide and is considered to be an economically important pest. Little is known about the digestive enzymes such as serine proteases (SPs) in B. dorsalis, which are important both
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The oriental fruit fly Bactrocera dorsalis (Hendel) causes devastating losses to agricultural crops world-wide and is considered to be an economically important pest. Little is known about the digestive enzymes such as serine proteases (SPs) in B. dorsalis, which are important both for energy supply and mitigation of fitness cost associated with insecticide tolerance. In this study, we identified five SP genes in the midgut of B. dorsalis, and the alignments of their deduced amino acid sequences revealed the presence of motifs conserved in the SP superfamily. Phylogenetic analyses with known SPs from other insect species suggested that three of them were trypsin-like proteases. Analyses of the expression profiles among the different developmental stages showed that all five genes were most abundant in larvae than in other stages. When larvae were continuously fed on diet containing 0.33 μg/g β-Cypermethrin, expression of all five genes were upregulated in the midgut but the larval development was delayed. Biochemical assays were consistent with the increased protease activity exhibited by SPs in the midgut after treatment with β-Cypermethrin. Taken together, these findings provide evidence for the hypothesis that enhanced SP activity may play an indirect role in relieving the toxicity stress of insecticide in B. dorsalis. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessReview miR-137: A New Player in Schizophrenia
Int. J. Mol. Sci. 2014, 15(2), 3262-3271; https://doi.org/10.3390/ijms15023262
Received: 12 January 2014 / Revised: 12 February 2014 / Accepted: 14 February 2014 / Published: 21 February 2014
Cited by 32 | PDF Full-text (394 KB) | HTML Full-text | XML Full-text
Abstract
Schizophrenia is a complex genetic disease and characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment and adult neuronal processes by modulating the activity of multiple genes within biological networks. MiR-137 as
[...] Read more.
Schizophrenia is a complex genetic disease and characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are critical to neurodevelopment and adult neuronal processes by modulating the activity of multiple genes within biological networks. MiR-137 as a brain-enriched microRNA, plays important roles in regulating embryonic neural stem cells (NSCs) fate determination, neuronal proliferation and differentiation, and synaptic maturation. Its dysregulation causes changes in the gene expression regulation network of the nervous system, thus inducing mental disorders. Recently, miR-137 has been confirmed as a gene related to schizophrenia susceptibility. In the following review, we summarize the expression pattern, epigenetic regulation and functions of miR-137. A more complete picture of the miR-137, which is dysregulated in psychiatric illness, may improve our understanding of the molecular mechanisms underlying schizophrenia. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessCommunication Rationalization of Activity Cliffs of a Sulfonamide Inhibitor of DNA Methyltransferases with Induced-Fit Docking
Int. J. Mol. Sci. 2014, 15(2), 3253-3261; https://doi.org/10.3390/ijms15023253
Received: 14 January 2014 / Revised: 12 February 2014 / Accepted: 14 February 2014 / Published: 21 February 2014
Cited by 16 | PDF Full-text (723 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of
[...] Read more.
Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure–activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of ‘activity cliffs’, e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay. Full article
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Open AccessReview The Neuroprotective Role of Acupuncture and Activation of the BDNF Signaling Pathway
Int. J. Mol. Sci. 2014, 15(2), 3234-3252; https://doi.org/10.3390/ijms15023234
Received: 28 November 2013 / Revised: 8 February 2014 / Accepted: 10 February 2014 / Published: 21 February 2014
Cited by 21 | PDF Full-text (480 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have been conducted to examine the neuroprotective effects of acupuncture in many neurological disorders. Although the neuroprotective effects of acupuncture has been linked to changes in signaling pathways, accumulating evidence suggest the participation of endogenous biological mediators, such as the neurotrophin
[...] Read more.
Recent studies have been conducted to examine the neuroprotective effects of acupuncture in many neurological disorders. Although the neuroprotective effects of acupuncture has been linked to changes in signaling pathways, accumulating evidence suggest the participation of endogenous biological mediators, such as the neurotrophin (NT) family of proteins, specifically, the brain derived neurotrophic factor (BDNF). Accordingly, acupuncture can inhibit neurodegeneration via expression and activation of BDNF. Moreover, recent studies have reported that acupuncture can increase ATP levels at local stimulated points. We have also demonstrated that acupuncture could activate monocytes and increase the expression of BDNF via the stimulation of ATP. The purpose of this article is to review the recent findings and ongoing studies on the neuroprotective roles of acupuncture and therapeutic implications of acupuncture-induced activation of BDNF and its signaling pathway. Full article
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
Open AccessArticle Prediction of Protein–Protein Interaction with Pairwise Kernel Support Vector Machine
Int. J. Mol. Sci. 2014, 15(2), 3220-3233; https://doi.org/10.3390/ijms15023220
Received: 1 January 2014 / Revised: 27 January 2014 / Accepted: 29 January 2014 / Published: 21 February 2014
Cited by 23 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
Protein–protein interactions (PPIs) play a key role in many cellular processes. Unfortunately, the experimental methods currently used to identify PPIs are both time-consuming and expensive. These obstacles could be overcome by developing computational approaches to predict PPIs. Here, we report two methods of
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Protein–protein interactions (PPIs) play a key role in many cellular processes. Unfortunately, the experimental methods currently used to identify PPIs are both time-consuming and expensive. These obstacles could be overcome by developing computational approaches to predict PPIs. Here, we report two methods of amino acids feature extraction: (i) distance frequency with PCA reducing the dimension (DFPCA) and (ii) amino acid index distribution (AAID) representing the protein sequences. In order to obtain the most robust and reliable results for PPI prediction, pairwise kernel function and support vector machines (SVM) were employed to avoid the concatenation order of two feature vectors generated with two proteins. The highest prediction accuracies of AAID and DFPCA were 94% and 93.96%, respectively, using the 10 CV test, and the results of pairwise radial basis kernel function are considerably improved over those based on radial basis kernel function. Overall, the PPI prediction tool, termed PPI-PKSVM, which is freely available at http://159.226.118.31/PPI/index.html, promises to become useful in such areas as bio-analysis and drug development. Full article
Open AccessArticle A New Pepstatin-Insensitive Thermopsin-Like Protease Overproduced in Peptide-Rich Cultures of Sulfolobus solfataricus
Int. J. Mol. Sci. 2014, 15(2), 3204-3219; https://doi.org/10.3390/ijms15023204
Received: 5 December 2013 / Revised: 26 January 2014 / Accepted: 11 February 2014 / Published: 21 February 2014
Cited by 2 | PDF Full-text (859 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, we gain insight into the extracellular proteolytic system of Sulfolobus solfataricus grown on proteinaceous substrates, providing further evidence that acidic proteases were specifically produced in response to peptide-rich media. The main proteolytic component was the previously isolated SsMTP (Sulfolobus
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In this study, we gain insight into the extracellular proteolytic system of Sulfolobus solfataricus grown on proteinaceous substrates, providing further evidence that acidic proteases were specifically produced in response to peptide-rich media. The main proteolytic component was the previously isolated SsMTP (Sulfolobus solfataricus multi-domain thermopsin-like protease), while the less abundant (named SsMTP-1) one was purified, characterized and identified as the sso1175 gene-product. The protein revealed a multi-domain organization shared with the cognate SsMTP with a catalytic domain followed by several tandemly-repeated motifs. Moreover, both enzymes were found spread across the Crenarchaeota phylum and belonging to the thermopsin family, although segregated into diverse phylogenetic clusters. SsMTP-1 showed a 75-kDa molecular mass and was stable in the temperature range 50–90 °C, with optimal activity at 70 °C and pH 2.0. Serine, metallo and aspartic protease inhibitors did not affect the enzyme activity, designating SsMTP-1 as a new member of the pepstatin-insensitive aspartic protease family. The peptide-bond-specificity of SsMTP-1 in the cleavage of the oxidized insulin B chain was uncommon amongst thermopsins, suggesting that it could play a distinct, but cooperative role in the protein degradation machinery. Interestingly, predictions of the transmembrane protein topology of SsMTP and SsMTP-1 strongly suggest a possible contribution in signal-transduction pathways. Full article
(This article belongs to the Special Issue Thermophilic DNases, RNases and Proteases)
Open AccessArticle Pattern Recognition Techniques Applied to the Study of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase Inhibition
Int. J. Mol. Sci. 2014, 15(2), 3186-3203; https://doi.org/10.3390/ijms15023186
Received: 13 August 2013 / Revised: 21 January 2014 / Accepted: 24 January 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemometric pattern recognition techniques were employed in order to obtain Structure-Activity Relationship (SAR) models relating the structures of a series of adenosine compounds to the affinity for glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). A training set of 49 compounds was
[...] Read more.
Chemometric pattern recognition techniques were employed in order to obtain Structure-Activity Relationship (SAR) models relating the structures of a series of adenosine compounds to the affinity for glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). A training set of 49 compounds was used to build the models and the best ones were obtained with one geometrical and four electronic descriptors. Classification models were externally validated by predictions for a test set of 14 compounds not used in the model building process. Results of good quality were obtained, as verified by the correct classifications achieved. Moreover, the results are in good agreement with previous SAR studies on these molecules, to such an extent that we can suggest that these findings may help in further investigations on ligands of LmGAPDH capable of improving treatment of leishmaniasis. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Dynamin-Related Protein 1 Inhibitors Protect against Ischemic Toxicity through Attenuating Mitochondrial Ca2+ Uptake from Endoplasmic Reticulum Store in PC12 Cells
Int. J. Mol. Sci. 2014, 15(2), 3172-3185; https://doi.org/10.3390/ijms15023172
Received: 7 January 2014 / Revised: 25 January 2014 / Accepted: 27 January 2014 / Published: 21 February 2014
Cited by 4 | PDF Full-text (1733 KB) | HTML Full-text | XML Full-text
Abstract
Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction
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Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A) and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1), in neuronal injury induced by oxygen-glucose deprivation (OGD) in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP). Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca2+ uptake, but had no effect on cytoplasmic Ca2+ after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER) Ca2+ release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca2+ uptake from the ER store and attenuating mitochondrial dysfunction. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessArticle Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
Int. J. Mol. Sci. 2014, 15(2), 3154-3171; https://doi.org/10.3390/ijms15023154
Received: 27 December 2013 / Revised: 13 February 2014 / Accepted: 14 February 2014 / Published: 21 February 2014
Cited by 17 | PDF Full-text (1761 KB) | HTML Full-text | XML Full-text
Abstract
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus
[...] Read more.
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate the underlying mechanism, we found that evodiamine significantly reduced the protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression of this molecule attenuated the apoptosis induced by evodiamine alone, or in combination with TRAIL. Further experiments revealed that evodiamine did not affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually regulates protein translation; moreover, knockdown of S6K1 with small interfering RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these findings provide a rationale for the combined application of evodiamine with TRAIL in the treatment of bladder cancer. Full article
(This article belongs to the Special Issue Molecular Research in Urology 2014)
Open AccessReview Autophagic Cell Death and Cancer
Int. J. Mol. Sci. 2014, 15(2), 3145-3153; https://doi.org/10.3390/ijms15023145
Received: 6 January 2014 / Revised: 10 February 2014 / Accepted: 13 February 2014 / Published: 21 February 2014
Cited by 64 | PDF Full-text (462 KB) | HTML Full-text | XML Full-text
Abstract
Programmed cell death (PCD) is a crucial process required for the normal development and physiology of metazoans. The three major mechanisms that induce PCD are called type I (apoptosis), type II (autophagic cell death), and type III (necrotic cell death). Dysfunctional PCD leads
[...] Read more.
Programmed cell death (PCD) is a crucial process required for the normal development and physiology of metazoans. The three major mechanisms that induce PCD are called type I (apoptosis), type II (autophagic cell death), and type III (necrotic cell death). Dysfunctional PCD leads to diseases such as cancer and neurodegeneration. Although apoptosis is the most common form of PCD, recent studies have provided evidence that there are other forms of cell death. One of such cell death is autophagic cell death, which occurs via the activation of autophagy. The present review summarizes recent knowledge about autophagic cell death and discusses the relationship with tumorigenesis. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessReview Genetics of Oxidative Stress in Obesity
Int. J. Mol. Sci. 2014, 15(2), 3118-3144; https://doi.org/10.3390/ijms15023118
Received: 15 January 2014 / Revised: 12 February 2014 / Accepted: 12 February 2014 / Published: 20 February 2014
Cited by 22 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen
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Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications. Full article
(This article belongs to the Special Issue Nutritional Control of Metabolism)
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