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Int. J. Mol. Sci., Volume 15, Issue 1 (January 2014), Pages 1-1685

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Open AccessEditorial International Journal of Molecular Science Best Paper Award 2014
Int. J. Mol. Sci. 2014, 15(1), 1683-1685; https://doi.org/10.3390/ijms15011683
Received: 20 January 2014 / Revised: 20 January 2014 / Accepted: 21 January 2014 / Published: 22 January 2014
Cited by 3 | PDF Full-text (145 KB) | HTML Full-text | XML Full-text
Abstract
International Journal of Molecular Science is instituting an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology published in International Journal of Molecular Science. We are pleased to announce the third “International Journal of
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International Journal of Molecular Science is instituting an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology published in International Journal of Molecular Science. We are pleased to announce the third “International Journal of Molecular Science Best Paper Award” for 2014 [1,2]. Nominations were made by the Section Editors-in-Chief of International Journal of Molecular Science from all papers published in 2010. [...] Full article
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Open AccessArticle The hOGG1 Ser326Cys Gene Polymorphism and the Risk of Coronary Ectasia in the Chinese Population
Int. J. Mol. Sci. 2014, 15(1), 1671-1682; https://doi.org/10.3390/ijms15011671
Received: 14 November 2013 / Revised: 6 January 2014 / Accepted: 20 January 2014 / Published: 22 January 2014
Cited by 7 | PDF Full-text (314 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress (OS) is related to vascular inflammation possibly, contributing to the development of coronary ectasia (CE). Base excision repair (BER) and nucleotide excision repair are the main DNA repair pathways that can help to remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human
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Oxidative stress (OS) is related to vascular inflammation possibly, contributing to the development of coronary ectasia (CE). Base excision repair (BER) and nucleotide excision repair are the main DNA repair pathways that can help to remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key enzyme of the BER pathway and catalyzes the removal of 8-OHdG. The aim of our study was to investigate the association between hOGG1 Ser326Cys gene polymorphism and CE in a Chinese population. Five-hundred forty-seven patients who underwent diagnostic coronary angiography in a tertiary medical center were recruited. The angiographic definition of CE is the diameter of the ectatic segment being more than 1.5 times larger compared with an adjacent healthy reference segment. The gene polymorphisms were analyzed by polymerase chain reaction. The urine 8OHdG concentration was measured using a commercial ELISA kit. The distribution of hOGG1 Ser326Cys genotypes was significantly different between CE and non-CE groups (p = 0.033). The odds ratio of CE development for the Ser to the Cys variant was 1.55 (95% confidence interval (CI), 1.04–2.31, p = 0.033). Both univariate and logistic regression analysis showed a significant association of hOGG1 Ser326Cys polymorphism in the dominant model with CE development (p = 0.009 and 0.011, respectively). Urine 8-OHdG levels were significantly higher in subjects carrying the hOGG1 Ser variant than in those with the Cys/Cys genotype (p < 0.03). In conclusion, our study suggests that the hOGG1 Ser326Cys gene variant might play a role in susceptibility to the development of CE. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessReview Signaling Involved in Hair Follicle Morphogenesis and Development
Int. J. Mol. Sci. 2014, 15(1), 1647-1670; https://doi.org/10.3390/ijms15011647
Received: 10 August 2013 / Revised: 21 October 2013 / Accepted: 22 October 2013 / Published: 22 January 2014
Cited by 49 | PDF Full-text (415 KB) | HTML Full-text | XML Full-text
Abstract
Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem
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Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessArticle Resveratrol Partially Prevents Rotenone-Induced Neurotoxicity in Dopaminergic SH-SY5Y Cells through Induction of Heme Oxygenase-1 Dependent Autophagy
Int. J. Mol. Sci. 2014, 15(1), 1625-1646; https://doi.org/10.3390/ijms15011625
Received: 11 November 2013 / Revised: 8 January 2014 / Accepted: 14 January 2014 / Published: 22 January 2014
Cited by 58 | PDF Full-text (1283 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative stress or protein misfolding and aggregation may underlie this process. Autophagy is an intracellular catabolic mechanism responsible for protein degradation and recycling of damaged
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Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative stress or protein misfolding and aggregation may underlie this process. Autophagy is an intracellular catabolic mechanism responsible for protein degradation and recycling of damaged proteins and cytoplasmic organelles. Autophagic dysfunction may hasten the progression of neuronal degeneration. In this study, resveratrol promoted autophagic flux and protected dopaminergic neurons against rotenone-induced apoptosis. In an in vivo PD model, rotenone induced loss of dopaminergic neurons, increased oxidation of mitochondrial proteins and promoted autophagic vesicle development in brain tissue. The natural phytoalexin resveratrol prevented rotenone-induced neuronal apoptosis in vitro, and this pro-survival effect was abolished by an autophagic inhibitor. Although both rotenone and resveratrol promoted LC3-II accumulation, autophagic flux was inhibited by rotenone and augmented by resveratrol. Further, rotenone reduced heme oxygenase-1 (HO-1) expression, whereas resveratrol increased HO-1 expression. Pharmacological inhibition of HO-1 abolished resveratrol-mediated autophagy and neuroprotection. Notably, the effects of a pharmacological inducer of HO-1 were similar to those of resveratrol, and protected against rotenone-induced cell death in an autophagy-dependent manner, validating the hypothesis of HO-1 dependent autophagy in preventing neuronal death in the in vitro PD model. Collectively, our findings suggest that resveratrol induces HO-1 expression and prevents dopaminergic cell death by regulating autophagic flux; thus protecting against rotenone-induced neuronal apoptosis. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
Open AccessArticle Intravitreal Injection of Ranibizumab and CTGF shRNA Improves Retinal Gene Expression and Microvessel Ultrastructure in a Rodent Model of Diabetes
Int. J. Mol. Sci. 2014, 15(1), 1606-1624; https://doi.org/10.3390/ijms15011606
Received: 1 November 2013 / Revised: 10 January 2014 / Accepted: 13 January 2014 / Published: 22 January 2014
Cited by 26 | PDF Full-text (4268 KB) | HTML Full-text | XML Full-text
Abstract
Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore,
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Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE)
Int. J. Mol. Sci. 2014, 15(1), 1590-1605; https://doi.org/10.3390/ijms15011590
Received: 9 December 2013 / Revised: 3 January 2014 / Accepted: 6 January 2014 / Published: 22 January 2014
Cited by 12 | PDF Full-text (1066 KB) | HTML Full-text | XML Full-text
Abstract
One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life
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One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species. Full article
(This article belongs to the Special Issue Interaction between Nano-Structure Materials and Cells)
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Open AccessArticle Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma
Int. J. Mol. Sci. 2014, 15(1), 1574-1589; https://doi.org/10.3390/ijms15011574
Received: 25 November 2013 / Revised: 16 December 2013 / Accepted: 3 January 2014 / Published: 21 January 2014
Cited by 11 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text
Abstract
Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported
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Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported two distinct effects of estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells proliferation: (1) an antiproliferative effect via a classical estrogen receptor beta-dependent pathway, and (2) a promotive effect via a non-classical membrane G-protein-coupled receptor, GPR30/GPER, which is only overexpressed in seminomas, the most common TGCT. In order to explain this overexpression, we investigated the possible association of polymorphisms in the GPER gene by using allele-specific tetra-primer polymerase chain reaction performed on tissue samples from 150 paraffin-embedded TGCT specimens (131 seminomas, 19 non seminomas). Compared to control population, loss of homozygous ancestral genotype GG in two polymorphisms located in the promoter region of GPER (rs3808350 and rs3808351) was more frequent in seminomas but not in non-seminomas (respectively, OR = 1.960 (1.172–3.277) and 7.000 (2.747–17.840); p < 0.01). These polymorphisms may explain GPER overexpression and represent a genetic factor of susceptibility supporting the contribution of environmental GPER ligands in testicular carcinogenesis. Full article
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
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Open AccessArticle Phosphorylation of Histone H2AX in the Mouse Brain from Development to Senescence
Int. J. Mol. Sci. 2014, 15(1), 1554-1573; https://doi.org/10.3390/ijms15011554
Received: 12 November 2013 / Revised: 30 December 2013 / Accepted: 10 January 2014 / Published: 21 January 2014
Cited by 6 | PDF Full-text (2771 KB) | HTML Full-text | XML Full-text
Abstract
Phosphorylation of the histone H2AX (γH2AX form) is an early response to DNA damage and a marker of aging and disease in several cells and tissues outside the nervous system. Little is known about in vivo phosphorylation of H2AX in neurons, although it
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Phosphorylation of the histone H2AX (γH2AX form) is an early response to DNA damage and a marker of aging and disease in several cells and tissues outside the nervous system. Little is known about in vivo phosphorylation of H2AX in neurons, although it was suggested that γH2AX is an early marker of neuronal endangerment thus opening the possibility to target it as a neuroprotective strategy. After experimental labeling of DNA-synthesizing cells with 5-bromo-2-deoxyuridine (BrdU), we studied the brain occurrence of γH2AX in developing, postnatal, adult and senescent (2 years) mice by light and electron microscopic immunocytochemistry and Western blotting. Focal and/or diffuse γH2AX immunostaining appears in interkinetic nuclei, mitotic chromosomes, and apoptotic nuclei. Immunoreactivity is mainly associated with neurogenetic areas, i.e., the subventricular zone (SVZ) of telencephalon, the cerebellar cortex, and, albeit to a much lesser extent, the subgranular zone of the hippocampal dentate gyrus. In addition, γH2AX is highly expressed in the adult and senescent cerebral cortex, particularly the piriform cortex. Double labeling experiments demonstrate that γH2AX in neurogenetic brain areas is temporally and functionally related to proliferation and apoptosis of neuronal precursors, i.e., the type C transit amplifying cells (SVZ) and the granule cell precursors (cerebellum). Conversely, γH2AX-immunoreactive cortical neurons incorporating the S phase-label BrdU do not express the proliferation marker phosphorylated histone H3, indicating that these postmitotic cells undergo a significant DNA damage response. Our study paves the way for a better comprehension of the role of H2AX phosphorylation in the normal brain, and offers additional data to design novel strategies for the protection of neuronal precursors and mature neurons in central nervous system (CNS) degenerative diseases. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
Open AccessArticle Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
Int. J. Mol. Sci. 2014, 15(1), 1538-1553; https://doi.org/10.3390/ijms15011538
Received: 9 December 2013 / Revised: 21 December 2013 / Accepted: 13 January 2014 / Published: 21 January 2014
Cited by 16 | PDF Full-text (1380 KB) | HTML Full-text | XML Full-text
Abstract
The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple
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The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessArticle Role of Insulin-Transferrin-Selenium in Auricular Chondrocyte Proliferation and Engineered Cartilage Formation in Vitro
Int. J. Mol. Sci. 2014, 15(1), 1525-1537; https://doi.org/10.3390/ijms15011525
Received: 26 November 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 21 January 2014
Cited by 10 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS) on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations
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The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS) on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%), or 10% FBS alone as a control for four weeks. Parameters including cell proliferation in monolayer, wet weight, collagen type I/II/X (Col I, II, X) and glycosaminoglycan (GAG) expression, GAG content of pellets and gene expression associated with cartilage formation/dedifferentiation (lost cartilage phenotype)/hypertrophy within the chondrocyte pellets were assessed. The results showed that chondrocytes proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS) in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone group. Furthermore, ITS prevented engineered cartilage from dedifferentiation (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan) and hypertrophy (i.e., lower mRNA expression of Col X and MMP13). In conclusion, our results indicated that ITS efficiently enhanced auricular chondrocytes proliferation, retained chondrogenic phenotypes, and promoted engineered cartilage formation when combined with FBS, which is potentially used as key supplementation in auricular chondrocytes and engineered cartilage culture. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Temperature-Responsive Poly(ε-caprolactone) Cell Culture Platform with Dynamically Tunable Nano-Roughness and Elasticity for Control of Myoblast Morphology
Int. J. Mol. Sci. 2014, 15(1), 1511-1524; https://doi.org/10.3390/ijms15011511
Received: 6 December 2013 / Revised: 15 January 2014 / Accepted: 16 January 2014 / Published: 21 January 2014
Cited by 22 | PDF Full-text (1154 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We developed a dynamic cell culture platform with dynamically tunable nano-roughness and elasticity. Temperature-responsive poly(ε-caprolactone) (PCL) films were successfully prepared by crosslinking linear and tetra-branched PCL macromonomers. By optimizing the mixing ratios, the crystal-amorphous transition temperature (Tm) of the crosslinked
[...] Read more.
We developed a dynamic cell culture platform with dynamically tunable nano-roughness and elasticity. Temperature-responsive poly(ε-caprolactone) (PCL) films were successfully prepared by crosslinking linear and tetra-branched PCL macromonomers. By optimizing the mixing ratios, the crystal-amorphous transition temperature (Tm) of the crosslinked film was adjusted to the biological relevant temperature (~33 °C). While the crosslinked films are relatively stiff (50 MPa) below the Tm, they suddenly become soft (1 MPa) above the Tm. Correspondingly, roughness of the surface was decreased from 63.4–12.4 nm. It is noted that the surface wettability was independent of temperature. To investigate the role of dynamic surface roughness and elasticity on cell adhesion, cells were seeded on PCL films at 32 °C. Interestingly, spread myoblasts on the film became rounded when temperature was suddenly increased to 37 °C, while significant changes in cell morphology were not observed for fibroblasts. These results indicate that cells can sense dynamic changes in the surrounding environment but the sensitivity depends on cell types. Full article
(This article belongs to the Special Issue Interaction between Nano-Structure Materials and Cells)
Open AccessArticle Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism
Int. J. Mol. Sci. 2014, 15(1), 1499-1510; https://doi.org/10.3390/ijms15011499
Received: 16 November 2013 / Revised: 12 December 2013 / Accepted: 7 January 2014 / Published: 21 January 2014
Cited by 4 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text
Abstract
Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral
[...] Read more.
Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen
Int. J. Mol. Sci. 2014, 15(1), 1481-1498; https://doi.org/10.3390/ijms15011481
Received: 30 November 2013 / Revised: 8 January 2014 / Accepted: 13 January 2014 / Published: 21 January 2014
Cited by 6 | PDF Full-text (1442 KB) | HTML Full-text | XML Full-text
Abstract
The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine
[...] Read more.
The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine. Full article
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
Open AccessArticle Plant Dependence on Rhizobia for Nitrogen Influences Induced Plant Defenses and Herbivore Performance
Int. J. Mol. Sci. 2014, 15(1), 1466-1480; https://doi.org/10.3390/ijms15011466
Received: 19 November 2013 / Revised: 15 January 2014 / Accepted: 15 January 2014 / Published: 21 January 2014
Cited by 11 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text
Abstract
Symbiotic rhizobia induce many changes in legumes that could affect aboveground interactions with herbivores. We explored how changing the intensity of Bradyrhizobium japonicum, as modulated by soil nitrogen (N) levels, influenced the interaction between soybean (Glycine max) and herbivores of
[...] Read more.
Symbiotic rhizobia induce many changes in legumes that could affect aboveground interactions with herbivores. We explored how changing the intensity of Bradyrhizobium japonicum, as modulated by soil nitrogen (N) levels, influenced the interaction between soybean (Glycine max) and herbivores of different feeding guilds. When we employed a range of fertilizer applications to manipulate soil N, plants primarily dependent on rhizobia for N exhibited increased root nodulation and higher levels of foliar ureides than plants given N fertilizer; yet all treatments maintained similar total N levels. Soybean podworm (Helicoverpa zea) larvae grew best on plants with the highest levels of rhizobia but, somewhat surprisingly, preferred to feed on high-N-fertilized plants when given a choice. Induction of the defense signaling compound jasmonic acid (JA) by H. zea feeding damage was highest in plants primarily dependent on rhizobia. Differences in rhizobial dependency on soybean did not appear to affect interactions with the phloem-feeding soybean aphid (Aphis glycines). Overall, our results suggest that rhizobia association can affect plant nutritional quality and the induction of defense signaling pathways and that these effects may influence herbivore feeding preferences and performance—though such effects may vary considerably for different classes of herbivores. Full article
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Open AccessReview Secondary Plant Products Causing Photosensitization in Grazing Herbivores: Their Structure, Activity and Regulation
Int. J. Mol. Sci. 2014, 15(1), 1441-1465; https://doi.org/10.3390/ijms15011441
Received: 15 December 2013 / Revised: 31 December 2013 / Accepted: 14 January 2014 / Published: 21 January 2014
Cited by 21 | PDF Full-text (537 KB) | HTML Full-text | XML Full-text
Abstract
Photosensitivity in animals is defined as a severe dermatitis that results from a heightened reactivity of skin cells and associated dermal tissues upon their exposure to sunlight, following ingestion or contact with UV reactive secondary plant products. Photosensitivity occurs in animal cells as
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Photosensitivity in animals is defined as a severe dermatitis that results from a heightened reactivity of skin cells and associated dermal tissues upon their exposure to sunlight, following ingestion or contact with UV reactive secondary plant products. Photosensitivity occurs in animal cells as a reaction that is mediated by a light absorbing molecule, specifically in this case a plant-produced metabolite that is heterocyclic or polyphenolic. In sensitive animals, this reaction is most severe in non-pigmented skin which has the least protection from UV or visible light exposure. Photosensitization in a biological system such as the epidermis is an oxidative or other chemical change in a molecule in response to light-induced excitation of endogenous or exogenously-delivered molecules within the tissue. Photo-oxidation can also occur in the plant itself, resulting in the generation of reactive oxygen species, free radical damage and eventual DNA degradation. Similar cellular changes occur in affected herbivores and are associated with an accumulation of photodynamic molecules in the affected dermal tissues or circulatory system of the herbivore. Recent advances in our ability to identify and detect secondary products at trace levels in the plant and surrounding environment, or in organisms that ingest plants, have provided additional evidence for the role of secondary metabolites in photosensitization of grazing herbivores. This review outlines the role of unique secondary products produced by higher plants in the animal photosensitization process, describes their chemistry and localization in the plant as well as impacts of the environment upon their production, discusses their direct and indirect effects on associated animal systems and presents several examples of well-characterized plant photosensitization in animal systems. Full article
(This article belongs to the Section Molecular Toxicology)
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