Publications by authors named "Goo-Bo Jeong"

18 Publications

  • Page 1 of 1

Mesenchymal Stem Cell-Derived Exosomes Exhibit Promising Potential for Treating SARS-CoV-2-Infected Patients.

Cells 2021 03 7;10(3). Epub 2021 Mar 7.

Department of Anatomy and Cell Biology, College of Medicine, Gachon University, 155 Getbeol-ro, Yeonsu-gu, Incheon 21999, Korea.

The novel coronavirus severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) is responsible for COVID-19 infection. The COVID-19 pandemic represents one of the worst global threats in the 21st century since World War II. This pandemic has led to a worldwide economic recession and crisis due to lockdown. Biomedical researchers, pharmaceutical companies, and premier institutes throughout the world are claiming that new clinical trials are in progress. During the severe phase of this disease, mechanical ventilators are used to assist in the management of outcomes; however, their use can lead to the development of pneumonia. In this context, mesenchymal stem cell (MSC)-derived exosomes can serve as an immunomodulation treatment for COVID-19 patients. Exosomes possess anti-inflammatory, pro-angiogenic, and immunomodulatory properties that can be explored in an effort to improve the outcomes of SARS-CoV-2-infected patients. Currently, only one ongoing clinical trial (NCT04276987) is specifically exploring the use of MSC-derived exosomes as a therapy to treat SARS-CoV-2-associated pneumonia. The purpose of this review is to provide insights of using exosomes derived from mesenchymal stem cells in management of the co-morbidities associated with SARS-CoV-2-infected persons in direction of improving their health outcome. There is limited knowledge of using exosomes in SARS-CoV-2; the clinicians and researchers should exploit exosomes as therapeutic regime.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10030587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001291PMC
March 2021

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinson’s Disease Model.

Int J Stem Cells 2019 Mar;12(1):114-124

Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.

Background And Objectives: Parkinson’s disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD.

Methods: The soluble RAGE (sRAGE) secreting Umbilical Cord Blood-derived Mesenchymal Stem Cell (UCB-MSC) was generated by gene editing method using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9). These cells were transplanted into Corpus Striatum of rotenone-induced PD animal models then behavioral test, morphological analysis, and immunohistochemical experiments were performed to determine the neuronal cell death and recovery of movement.

Results: The neuronal cell death in Corpus Striatum and Substantia Nigra was dramatically reduced and the movement was improved after sRAGE secreting UCB-MSC treatment in PD mice by inhibition of RAGE in neuronal cells.

Conclusions: We suggest that sRAGE secreting UCB-MSC based therapeutic approach could be a potential treatment strategy for neurodegenerative disease including PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15283/ijsc18110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457706PMC
March 2019

Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases.

Pharmacol Ther 2017 Sep 13;177:44-55. Epub 2017 Feb 13.

Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea; Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon 406-799, Republic of Korea. Electronic address:

Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways. AGEs inhibition has been shown to prevent the pathogenesis of AGEs-related diseases in human, and therapeutic advances have resulted in several agents that prevent their adverse effects. Recently, anti-inflammatory molecules that inhibit AGEs have been shown to be good candidates for ameliorating diabetic complications as well as degenerative diseases. This review was undertaken to present, discuss, and clarify current understanding regarding AGEs formation in association with macrophages, different diseases, therapeutic and diagnostic strategy and links with RAGE inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharmthera.2017.02.030DOI Listing
September 2017

Intravenously Infused F3.Olig2 Improves Memory Deficits via Restoring Myelination in the Aged Hippocampus Following Experimental Ischemic Stroke.

Cell Transplant 2016 12 20;25(12):2129-2144. Epub 2016 Jul 20.

Oligodendrocytes play a crucial role in creating the myelin sheath that is an important component in neural transmission. In an animal model of transient cerebral ischemia, application of oligodendrocyte progenitor cells (OPCs) has not yet been reported. In this study, the effects of F3.Olig2 transplantation on memory and cognitive dysfunction were investigated in the aged gerbil in which ischemic stroke was induced. To investigate the possible mechanisms underlying repair, changes in the expression of myelin basic protein (MBP), oligodendrocyte-specific protein (OSP), and brain-derived neurotrophic factor (BDNF) were examined. Experimental ischemic stroke was induced by occlusion of bilateral common carotid arteries in aged gerbils. Gerbils (n=31 per group) were randomly divided into three groups: (1) vehicle sham group, (2) vehicle ischemia group, and (3) F3.Olig2 ischemia group. After 1, 3, and 7 days of ischemiareperfusion (I-R), saline or F3.Olig2 cells (1106 cells in 100 l) were injected into the gerbils intravenously. The gerbils were sacrificed 10 days after I-R for identification of grafted F3.Olig2 cells, and 15 and 30 days after I-R for tissue analysis after conducting passive avoidance and novel object recognition test. Injected F3.Olig2 cells and MBP, OSP, and BDNF were detected by specific antibodies using immunohistochemistry and/or Western blots. Memory and cognition were significantly increased in the F3.Olig2 ischemia group compared with the vehicle ischemia group. In the F3.Olig2 ischemia group, the neurons were not protected from ischemic damage; however, MBP, OSP, and BDNF expressions were significantly increased. Our results show that injection of F3.Olig2 cells significantly improved impaired memory and cognition, which might be related to increased MBP expression via increasing OSP and BDNF expression in the aged gerbil hippocampus following transient cerebral ischemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3727/096368916X692230DOI Listing
December 2016

3D texture analysis in renal cell carcinoma tissue image grading.

Comput Math Methods Med 2014 9;2014:536217. Epub 2014 Oct 9.

Department of Computer Engineering, Inje University, Injero 197, UHRC, Gimhae, Gyeongnam 621-749, Republic of Korea.

One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM) and a 3D wavelet based on two types of basis functions. To evaluate their validity, we predefined 6 different statistical classifiers and applied these to the extracted feature sets. In the grade classification results, 3D Haar wavelet texture features combined with principal component analysis showed the best discrimination results. Classification using 3D wavelet texture features was significantly better than 3D GLCM, suggesting that the former has potential for use in a computer-based grading system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/536217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209774PMC
June 2015

BDNF expression of macrophages and angiogenesis after myocardial infarction.

Int J Cardiol 2014 Oct 8;176(3):1405-8. Epub 2014 Aug 8.

Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon 406-799, Republic of Korea. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2014.08.019DOI Listing
October 2014

Changes of calcium binding proteins, c-Fos and COX in hippocampal formation and cerebellum of Niemann-Pick, type C mouse.

J Chem Neuroanat 2013 Sep 6;52:1-8. Epub 2013 May 6.

Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, South Korea; Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon 406-799, South Korea.

Niemann-Pick disease, type C (NPC) is an intractable disease that is accompanied by ataxia, dystonia, neurodegeneration, and dementia due to an NPC gene defect. Disruption of calcium homeostasis in neurons is important in patients with NPC. Thus, we used immunohistochemistry to assess the expression levels of calcium binding proteins (calbindin D28K, parvalbumin, and calretinin), c-Fos and cyclooxygenase-1,2 (COX-1,2) in the hippocampal formation and cerebellum of 4 and 8 week old NPC+/+, NPC+/-, and NPC-/- mice. General expression of these proteins decreased in the hippocampus and cerebellum of NPC-/- compared to that in both young and adult NPC+/+ or NPC+/- mice. Parvalbumin, COX-1,2 or c-Fos-immunoreactive neurons were widely detected in the CA1, CA3, and DG of the hippocampus, but the immunoreactivities were decreased sharply in all areas of hippocampus of NPC-/- compared to NPC+/+ and NPC+/- mice. Taken together, reduction of these proteins may be one of the strong phenotypes related to the neuronal degeneration in NPC-/- mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchemneu.2013.04.006DOI Listing
September 2013

Caffeine-induced endothelial cell death and the inhibition of angiogenesis.

Anat Cell Biol 2013 Mar 25;46(1):57-67. Epub 2013 Mar 25.

Department of Anatomy, Chungbuk National University Medical School, Cheongju, Korea.

Numerous studies have shown that adenosine or adenosine agonists can stimulate angiogenesis. However, the effect of caffeine (a known adenosine receptor antagonist) on angiogenesis has not been previously studied. Accordingly, this study was undertaken to examine the effect of caffeine on angiogenesis and to clarify the mechanism involved. Chick chorioallantoic membrane assays were used to investigate the effect of caffeine on angiogenesis and proliferation assays using human umbilical vein endothelial cells (HUVECs), were used to study its effects on specific aspects of angiogenesis. The expressions of caspase-3 and Bcl-2 were examined by western blotting, immunofluorescence staining was used to identify HUVEC morphological changes, and fluorescence activated cell sorting (FACS) and DAPI staining were used to detect HUVEC apoptosis. Caffeine was found to inhibit blood vessel formation dose-dependently and to inhibit the proliferation of HUVECs time- and dose-dependently. FACS analysis and DAPI staining showed that inhibitory effect of caffeine on HUVEC proliferation was the result of apoptosis and the up-regulation of thrombospondin-1 (TSP-1). Furthermore, TSP-1 levels were down-regulated by NECA but were unaffected by CGS21680, indicating that caffeine regulated TSP-1 expression via adenosine A2B receptor. In addition, caffeine up-regulated caspase-3 and down-regulated Bcl-2 at the protein level. These results suggest that the inhibitory effect of caffeine on angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis, probably mediated by a caspase-3 dependent mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5115/acb.2013.46.1.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615613PMC
March 2013

Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen-activated protein kinase-dependent activation in human microglial cells.

Electrophoresis 2012 Dec 4;33(24):3756-63. Epub 2012 Dec 4.

Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.

Microglial cells act as the first and main form of active immune defense in the central nervous system related to inflammation and neurodegenerative disease. Lipopolysaccharide (LPS) induces many genes encoding inflammatory mediators, including cytokines such as tumor necrosis factor-α, interleukin-1β, (IL-1β), and IL-6, chemokines, and prostaglandins in microglial cells. Quantitative proteomics methods with isobaric chemical labeling using tandem mass tags and 2D-nano LC-ESI-MS/MS were used to systematically analyze proteomic changes in microglia responding to LPS stimulation. As a result, we found that the expression level of 21 proteins in human microglial cells changed after activation. Among those, one of the strong mitogen-activated protein kinase (MAPK) regulator proteins, CMPK1 was highly upregulated after LPS stimulation in human microglial cells. We detected and validated upregulation of MAPK including ERK1/2, p38, and SAPK/JNK by immunohistochemistry and Western blotting. NFκB, strong transcription factor of CMPK1, was translocated to the nucleus from the cytosol by high contents screening after LPS stimulation. Taken together, we conclude that MAPK signaling plays an important role in LPS-induced human microglial activation related to inflammatory response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/elps.201200345DOI Listing
December 2012

Activated microglial cells synthesize and secrete AGE-albumin.

Anat Cell Biol 2012 Mar 31;45(1):47-52. Epub 2012 Mar 31.

Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.

A holy grail of curing neurodegenerative diseases is to identify the main causes and mechanisms underlying neuronal death. Many studies have sought to identify these targets in a wide variety of ways, but a more important task is to identify critical molecular targets and their origins. Potential molecular targets include advanced glycation end products (AGEs) that can promote neuronal cell death, thereby contributing to neurodegenerative disorders such as Alzheimer disease or Parkinson disease. In this study, we showed that AGE-albumin (glycated albumin) is synthesized in microglial cells and secreted in the human brain. Our results provide new insight into which microglial cells can promote the receptor for AGE-mediated neuronal cell death, eventually leading to neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5115/acb.2012.45.1.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328740PMC
March 2012

Recovery of CNS pathway innervating the sciatic nerve following transplantation of human neural stem cells in rat spinal cord injury.

Cell Mol Neurobiol 2012 Jan 11;32(1):149-57. Epub 2011 Aug 11.

Department of Orthopedic Surgery, Chonbuk National University Medical School, Jeonju, 560-762, South Korea.

Stem cell research has been attained a greater attention in most fields of medicine due to its potential for many incurable diseases through replacing or helping the regeneration of damaged cells or tissues. Here, we demonstrated the functional recovery and structural connection of the central nervous system pathway innervating the sciatic nerve after total transection of the spinal cord followed by the transplantation of human neural stem cells (hNSC) in the injured rat spinal cord site. The limb function of hNSC-treated group recovered dramatically compared with that in the sham group by Basso-Beattie-Bresnahan (BBB) scores. Transplanted hNSC differentiated into astrocytes and neurons in the injured site. In addition, immunohistochemistry for growth-associated protein 43 showed axonal regeneration in the injured spinal cord site. The pseudorabies viral-Ba (PRV-Ba) tracing method revealed that transplanted hNSC and their differentiated neurons showed positive labeling after sciatic nerve injection. In addition, the PRV-Ba labeling was also observed in several nuclei in the brain innervating the sciatic nerve. This result implies that the rat CNS motor pathway could be reconstructed by hNSC transplantation, and it may contribute to the functional recovery of the limb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-011-9745-7DOI Listing
January 2012

Alteration of the CNS pathway to the hippocampus in a mouse model of Niemann-Pick, type C disease.

J Chem Neuroanat 2011 Sep 27;42(1):39-44. Epub 2011 Apr 27.

Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea.

Niemann-Pick type C disease (NPC) is an autosomal recessive disorder that results in premature death due to progressive neurodegeneration including dementia. To understand neuronal pathways connecting to the hippocampus, retrograde transneuronal labeling method with Bartha strain of pseudorabies virus (PRV) was employed in 40 NPC+/+, NPC+/- and NPC-/- mice. Immunohistochemistry using polyclonal antibody against PRV and streological counting were used. The number of neurons and synapse in CA2&3 regions of the hippocampus decreased dramatically in the NPC-/- mouse compared to the NPC+/+ or +/- mouse. The number of PRV positive cell was significantly decreased in several regions including the entorhinal and piriform cortex in the NPC-/- mouse. More severely, lateral septal dorsal nucleus, dorsal entorhinal cortex and medial geniculate body showed no positive labeling in the NPC-/- mouse. However, the hippocampus, medial septal and supramammilary nuclei showed increased immunoreactivity in the NPC-/- mouse. Our data suggest that the synaptic loss and discontinuity of the CNS hippocampal pathway may contribute to understanding the mechanism of symptoms and functional disabilities such as memory and learning disturbance in NPC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchemneu.2011.04.003DOI Listing
September 2011

Signaling events in axons and/or dendrites render motor neurons vulnerable to mutant superoxide dismutase toxicity.

J Neurosci 2011 Jan;31(1):295-9

Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

The survival of dorsal root ganglion and sympathetic neurons is promoted whether nerve growth factor (NGF) activates TrkA receptors on the cell body or the axon. Yet other aspects of neurotrophic factor actions (i.e., ability to promote axon growth, selection of neurochemical phenotype and engagement of signaling modules) differ as a function of the location of the ligand-receptor interaction. The extent to which these observations are relevant to CNS neurons is unknown. This may be particularly relevant to neurodegenerative diseases such as amyotrophic lateral sclerosis, where beneficial axon-target interactions are disturbed early in the disease process. Here we characterize the growth of pure motor neurons in compartment cultures and show that brain-derived neurotrophic factor (BDNF) stimulation of the cell body or axons/dendrites promotes survival. Expression of G37R mutant superoxide dismutase (SOD) in motor neurons will lead to death and this depends on BDNF activation of TrkB on axons and/or dendrites. BDNF action depends upon endocytosis of the BDNF-TrkB complex and de novo protein synthesis. These results highlight the importance of signaling events occurring in axons/dendrites in mutant SOD toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.4824-10.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091265PMC
January 2011

A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration.

J Neurosci 2009 Aug;29(31):9903-17

University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Retrograde axonal transport of cellular signals driven by dynein is vital for neuronal survival. Mouse models with defects in the retrograde transport machinery, including the Loa mouse (point mutation in dynein) and the Tg(dynamitin) mouse (overexpression of dynamitin), exhibit mild neurodegenerative disease. Transport defects have also been observed in more rapidly progressive neurodegeneration, such as that observed in the SOD1(G93A) transgenic mouse model for familial amyotrophic lateral sclerosis (ALS). Here, we test the hypothesis that alterations in retrograde signaling lead to neurodegeneration. In vivo, in vitro, and live-cell imaging motility assays show misregulation of transport and inhibition of retrograde signaling in the SOD1(G93A) model. However, similar inhibition is also seen in the Loa and Tg(dynamitin) mouse models. Thus, slowing of retrograde signaling leads only to mild degeneration and cannot explain ALS etiology. To further pursue this question, we used a proteomics approach to investigate dynein-associated retrograde signaling. These data indicate a significant decrease in retrograde survival factors, including P-Trk (phospho-Trk) and P-Erk1/2, and an increase in retrograde stress factor signaling, including P-JNK (phosphorylated c-Jun N-terminal kinase), caspase-8, and p75(NTR) cleavage fragment in the SOD1(G93A) model; similar changes are not seen in the Loa mouse. Cocultures of motor neurons and glia expressing mutant SOD1 (mSOD1) in compartmentalized chambers indicate that inhibition of retrograde stress signaling is sufficient to block activation of cellular stress pathways and to rescue motor neurons from mSOD1-induced toxicity. Hence, a shift from survival-promoting to death-promoting retrograde signaling may be key to the rapid onset of neurodegeneration seen in ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.0813-09.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095444PMC
August 2009

Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors.

J Neurosci 2006 Sep;26(36):9250-63

Department of Neurology, Children's Hospital of Philadelphia, Joseph Stokes Jr. Research Institute, Philadelphia, Pennsylvania 19104, USA.

The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs). Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide dismutase 1; G59S p150(glued)) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.1856-06.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674510PMC
September 2006

Bi-directional control of motor neuron dendrite remodeling by the calcium permeability of AMPA receptors.

Mol Cell Neurosci 2006 Jul 21;32(3):299-314. Epub 2006 Jun 21.

Department of Anatomy, College of Medicine, Chungbuk National University, Cheong-ju 361-763, Republic of Korea.

Motor neurons express particularly high levels of the AMPA receptor subunit GluR1(Q)flip (GluR1(Q)i) during the period in early postnatal life when their dendritic tree grows and becomes more branched. To investigate how GluR1-containing AMPA receptors contribute to dendrite morphogenesis, we characterized a mutant form of GluR1 (containing a histidine in the Q/R editing site) with unique electrophysiological properties. Most notably, AMPA receptors assembled from GluR1(H)i display less calcium permeability than AMPA receptors assembled from GluR1(Q)i. Expression of GluR1(Q)i in vivo or in vitro led to an increase in dendrite branching with no net change in the overall tree size while GluR1(H)i led to a loss of branches and a net reduction in overall tree size. GluR1(H)i-dependent dendrite atrophy is mediated by protein phosphatase 2B. The results suggest that the electrophysiological properties of cell surface AMPA receptors, specifically their permeability to calcium, can be a central determinant of whether the dendrites undergo activity-dependent branching or atrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mcn.2006.04.008DOI Listing
July 2006

Elevation of cyclin B1, active cdc2, and HuR in cervical neoplasia with human papillomavirus type 18 infection.

Cancer Lett 2006 Feb;232(2):170-8

Department of Pathology, Yonsei University College of Medicine, Seodaemoon-ku, Shinchon-dong 134, Seoul 120-752, South Korea.

Over 30 cervical epitheliotrophic HPV types may lead to altered biological functions that affect the clinical outcome of HPV infection. In order to determine the regulatory mechanism and effect of different HPV subtypes, we performed functional assays on cdc2, cyclinB1 and HuR in human uterine cervical samples. After confirming 22 HPV types among 95 cervical swabs, 10 cervical tissues, and seven established cell lines using a DNA chip, we evaluated the functional activities of G2 molecules assays, that included; western blotting for cyclin B1, cdc2 and phospho-cdc2 (Y15 and T161), immunoprecipitation for cdc2, a nuclear extraction fractional assay, and RT-PCR for cyclin B1. The expression of cyclin B1 was found to be dependent on HPV type, and was particularly overexpressed in high-risk types, whereas cdc2 was ubiquitously expressed irrespective of HPV type. Phospho-cdc2 and cyclin B1, however, were most intense in HPV18 infected cervical samples. Furthermore, the HuR stabilizing factor of the cyclin B1 transcript was upregulated in HPV 18 infected swabs. Moreover, SiHa cell line showed weaker G2 functional activity than the HeLa cell line. This study demonstrates that HPV-18 decreases the fidelity of mitotic checkpoints and increases cdc2-associated histone H1 kinase activity relative to control populations, and further shows that the G2 checkpoint is aberrant by virtue of the stabilization of cyclin B1 mRNA through the upregulation of HuR protein and the functional form of cdc2, especially in cases with HPV 18 infected cervical lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2005.02.026DOI Listing
February 2006

Expression pattern, regulation, and biological role of runt domain transcription factor, run, in Caenorhabditis elegans.

Mol Cell Biol 2002 Jan;22(2):547-54

Department of Biology, Yonsei University, Seoul 120-749, South Korea.

The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an essential role in osteogenesis, and inactivation of one allele of Runx2 is responsible for the human disease cleidocranial dysplasia. To understand the role of run in C. elegans, we used transgenic run::GFP reporter constructs and a double-stranded RNA-mediated interference method. The expression of run was detected as early as the bean stage exclusively in the nuclei of seam hypodermal cells and lasted until the L3 stage. At the larval stage, expression of run was additionally detected in intestinal cells. The regulatory elements responsible for the postembryonic hypodermal seam cells and intestinal cells were separately located within a 7.2-kb-long intron region. This is the first report demonstrating that an intron region is essential for stage-specific and cell type-specific expression of a C. elegans gene. RNA interference analysis targeting the run gene resulted in an early larva-lethal phenotype, with apparent malformation of the hypodermis and intestine. These results suggest that run is involved in the development of a functional hypodermis and gut in C. elegans. The highly conserved role of the Runt domain transcription factor in gut development during evolution from nematodes to mammals is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139740PMC
http://dx.doi.org/10.1128/mcb.22.2.547-554.2002DOI Listing
January 2002