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1.
Can J Neurol Sci ; 47(3): 344-349, 2020 05.
Article in English | MEDLINE | ID: mdl-31685057

ABSTRACT

BACKGROUND: Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson's disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment. METHODS: A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson's Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications. RESULTS: The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, -0.61 ± 0.61: -1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, -1.457 ± 1.078: -0.904 ± 0.812, p = 0.0018). CONCLUSIONS: Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.


Subject(s)
Auditory Cortex/physiopathology , Evoked Potentials, Auditory/physiology , Parkinson Disease/physiopathology , Serotonin/metabolism , Acoustic Stimulation , Age of Onset , Aged , Aged, 80 and over , Auditory Cortex/physiology , Dopamine Agents/therapeutic use , Electroencephalography , Female , Humans , Male , Middle Aged , Parkinson Disease/drug therapy , Synaptic Transmission/physiology
2.
Proc Natl Acad Sci U S A ; 109(26): 10214-7, 2012 Jun 26.
Article in English | MEDLINE | ID: mdl-22689954

ABSTRACT

Fluorescent small molecules have become indispensable tools for biomedical research along with the rapidly developing optical imaging technology. We report here a neural stem cell specific boron-dipyrromethane (BODIPY) derivative compound of designation red 3 (CDr3), developed through a high throughput/content screening of in-house generated diversity oriented fluorescence library in stem cells at different developmental stages. This novel compound specifically detects living neural stem cells of both human and mouse origin. Furthermore, we identified its binding target by proteomic analysis as fatty acid binding protein 7 (FABP7), also known as brain lipid binding protein) which is highly expressed in neural stem cells and localized in the cytoplasm. CDr3 will be a valuable chemical tool in the study and applications of neural stem cells.


Subject(s)
Carrier Proteins/metabolism , Fatty Acid-Binding Proteins/metabolism , Fluorescent Dyes/metabolism , Nerve Tissue Proteins/metabolism , Neural Stem Cells/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Cell Proliferation , Fatty Acid-Binding Protein 7 , Humans , Mice , Neural Stem Cells/cytology , Protein Binding
3.
Knee Surg Sports Traumatol Arthrosc ; 23(1): 97-103, 2015 Jan.
Article in English | MEDLINE | ID: mdl-23188498

ABSTRACT

PURPOSE: This study was undertaken to report clinical outcomes after high tibial osteotomy (HTO) in patients with a discoid lateral meniscus and to determine (1) whether discoid lateral meniscus degeneration by magnetic resonance imaging (MRI) progresses after HTO and (2) whether this progression adversely affects clinical results. METHODS: The records of 292 patients (292 knees) who underwent medial opening HTO were retrospectively reviewed, and discoid types and grades of lateral meniscus degeneration as determined by MRI were recorded preoperatively. Of the 292 patients, 17 (5.8%) had a discoid lateral meniscus, and postoperative MR images were obtained at least 2 years after HTO for 15 of these 17 patients. RESULTS: American Knee Society (AKS) pain, knee and function scores significantly improved in the 15 patients after surgery (p < 0.001). Eight (53%) had an incomplete and 7 (47%) had a complete discoid lateral meniscus. By preoperative MRI, the distribution of meniscal degeneration was as follows: grade 1, 4 patients; grade 2, 7 patients; and grade 3, 4 patients. At the final follow-up, the distribution of degeneration was as follows: grade 1, 2 patients; grade 2, 5 patients; and grade 3, 8 patients. Two patients with grade 3 degeneration who did not undergo partial meniscectomy showed tear progression. Thus, 8 of the 15 patients (53%) experienced progressive discoid meniscal degeneration after HTO. Median AKS pain score was significantly lower in the progression group than in the non-progression group (40 vs 45, respectively). CONCLUSION: The results of this study suggest that increased load on the lateral compartment after HTO can accelerate discoid lateral meniscus degeneration by MRI and caution that when a discoid lateral meniscus is found by preoperative MRI, progressive degeneration may occur after HTO and clinical outcome may be adversely affected. LEVEL OF EVIDENCE: Therapeutic study, Level IV.


Subject(s)
Cartilage Diseases/etiology , Knee Joint/surgery , Menisci, Tibial , Osteoarthritis, Knee/surgery , Osteotomy/adverse effects , Tibia/surgery , Cartilage Diseases/pathology , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Menisci, Tibial/pathology , Middle Aged , Pain/surgery , Retrospective Studies , Treatment Outcome
4.
Nat Genet ; 37(3): 305-10, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15731759

ABSTRACT

Several transient receptor potential channels were recently found to be activated by temperature stimuli in vitro. Their physiological and behavioral roles are largely unknown. From a temperature-preference behavior screen of 27,000 Drosophila melanogaster P-insertion mutants, we isolated a gene, named pyrexia (pyx), encoding a new transient receptor potential channel. Pyx was opened by temperatures above 40 degrees C in Xenopus laevis oocytes and HEK293T cells. It was ubiquitously expressed along the dendrites of a subset of peripheral nervous system neurons and was more permeable to K(+) than to Na(+). Although some pyx alleles resulted in abnormal temperature preferences, pyx null flies did not have significantly different temperature preferences than wild-type flies. But 60% of pyx null flies were paralyzed within 3 min of exposure to 40 degrees C, whereas only 9% of wild-type flies were paralyzed by the same stimulus. From these findings, we propose that the primary in vivo role of Pyx is to protect flies from high-temperature stress.


Subject(s)
Calmodulin-Binding Proteins/physiology , Drosophila Proteins/physiology , Drosophila melanogaster/physiology , Fever/physiopathology , Hot Temperature , Membrane Proteins/physiology , Amino Acid Sequence , Animals , Calmodulin-Binding Proteins/chemistry , Cell Line , Cloning, Molecular , DNA, Complementary , Drosophila Proteins/chemistry , Humans , Immunohistochemistry , Membrane Proteins/chemistry , Molecular Sequence Data , Sequence Homology, Amino Acid , Transient Receptor Potential Channels , Xenopus laevis
5.
J Microbiol Biotechnol ; 34(3): 654-662, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38213301

ABSTRACT

To investigate the effect of the predominant fungal species from Korean traditional meju and doenjang on soybean fermentation, the enzymatic activity and amino acid production of twenty-two fungal strains were assessed through solid- and liquid-state soybean fermentation. Enzymatic activity analyses of solid-state fermented soybeans revealed different enzyme activities involving protease, leucine aminopeptidase (LAP), carboxypeptidase (CaP), glutaminase, γ-glutamyl transferase (GGT), and amylase, depending on the fungal species. These enzymatic activities significantly affected the amino acid profile throughout liquid-state fermentation. Strains belonging to Mucoromycota, including Lichtheimia, Mucor, Rhizomucor, and Rhizopus, produced smaller amounts of total amino acids and umami-producing amino acids, such as glutamic acid and aspartic acid, than strains belonging to Aspergillus subgenus circumdati. The genera Penicillium and Scopulariopsis produced large amounts of total amino acids and glutamic acid, suggesting that these genera play an essential role in producing umami and kokumi tastes in fermented soybean products. Strains belonging to Aspergillus subgenus circumdati, including A. oryzae, showed the highest amino acid content, including glutamic acid, suggesting the potential benefits of A. oryzae as a starter for soybean fermentation. This study showed the potential of traditional meju strains as starters for soybean fermentation. However, further analysis of processes such as the production of G-peptide for kokumi taste and volatile compounds for flavor and safety is needed.


Subject(s)
Amino Acids , Soy Foods , Amino Acids/metabolism , Soy Foods/microbiology , Glycine max , Fermentation , Fungi , Aspergillus/metabolism , Glutamic Acid/metabolism , Peptide Hydrolases/metabolism
6.
Biochem Biophys Res Commun ; 406(3): 389-95, 2011 Mar 18.
Article in English | MEDLINE | ID: mdl-21329655

ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, including thiazolidinediones (TZDs), can induce anti-proliferation, differentiation, and apoptosis in various cancer cell types. This study investigated the mechanism of the anticancer effect of TZDs on human ovarian cancer. Six human ovarian cancer cell lines (NIH:OVCAR3, SKOV3, SNU-251, SNU-8, SNU-840, and 2774) were treated with the TZD, which induced dose-dependent inhibition of cell growth. Additionally, these cell lines exhibited various expression levels of PPARγ protein as revealed by Western blotting. Flow cytometry showed that the cell cycle was arrested at the G1 phase, as demonstrated by the appearance of a sub-G1 peak. This observation was corroborated by the finding of increased levels of Bax, p21, PARP, and cleaved caspase 3 in TGZ-treated cells. Interestingly, when we determined the effect of p53-induced growth inhibition in these three human ovarian cancer cells, we found that they either lacked p53 or contained a mutant form of p53. Furthermore, TGZ induced the expression of endogenous or exogenous p63 and p73 proteins and p63- or p73-directed short hairpin (si) RNAs inhibited the ability of TGZ to regulate expression of p21 in these cells. Thus, our results suggest that PPARγ ligands can induce growth suppression of ovarian cancer cells and mediate p63 and p73 expression, leading to enhanced growth inhibition and apoptosis. The tumor suppressive effects of PPARγ ligands may have applications for the treatment of ovarian cancer.


Subject(s)
Apoptosis , DNA-Binding Proteins/metabolism , Nuclear Proteins/metabolism , Ovarian Neoplasms/pathology , PPAR gamma/metabolism , Trans-Activators/metabolism , Tumor Suppressor Proteins/metabolism , Cell Cycle/genetics , Cell Line, Tumor , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Ligands , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Transcription Factors , Tumor Protein p73
7.
J Am Chem Soc ; 132(2): 576-9, 2010 Jan 20.
Article in English | MEDLINE | ID: mdl-20020712

ABSTRACT

During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library in C2C12 myogenesis, we discovered one compound that controls muscle differentiation. When treated to undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, and when treated to fully differentiated myotubes, it induced fission of multinucleated myotubes into mononucleated fragments. Compared to myoseverin, which is known for inducing myotube fission by destabilizing microtubules, B25 affects neither microtubule stability nor cell cycle. Further investigation identified that B25 induces myotube fission through the activation of NF-kappaB, which is one of the important signaling pathways linked to skeletal muscle differentiation. So far, the use of small-molecule fluorophores is limited in the discovery of labeling agents or sensors. In addition to their potential as a sensor, here we show the application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response.


Subject(s)
Cell Differentiation/drug effects , Fluorescent Dyes/metabolism , Fluorescent Dyes/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/drug effects , Animals , Cells, Cultured , Mice , Molecular Weight , Muscle Fibers, Skeletal/metabolism , PC12 Cells , Purines/pharmacology , Rats
8.
Cancer Sci ; 101(2): 482-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19922505

ABSTRACT

To overcome the low efficiency of gene therapy, we combined a conditionally replicating adenovirus (CRAd) and an adenoviral vector with a therapeutic gene. CRAd has an oncolytic activity in cancer cells with abnormal Rb activity and helps the replication of therapeutic genes incorporated in the E1-deleted adenovirus. We investigated the anticancer effect of a combination of CRAd and adenovirus carrying tumor necrosis factor-related apoptosis inducing ligand (ad-TRAIL). We expected to see increased gene expression in cancer cells as well as an antitumor effect. With the combined application of CRAd and ad-luciferase in head and neck cancer cell lines, we observed considerably increased luciferase activity that was 10- to 50-fold greater than with ad-luciferase alone. The combination of CRAd and ad-TRAIL showed significant suppression of growth in cell lines and increased the sub-G(1) portion of cells 30-fold compared to any single treatment. The expression of TRAIL was highly amplified by the combined treatment and was accompanied by expression of molecules related to apoptosis. In a xenograft animal model, mice treated with CRAd and ad-TRAIL showed complete regression of established tumors, whereas mice treated with CRAd or ad-TRAIL alone did not. In conclusion, this combined strategy using CRAd and adenovirus carrying a therapeutic gene increased the gene transfer rate and enhanced antitumor effects. We expect that this combination strategy could be extended to a multitarget cancer gene therapy by combining multiple adenoviruses and CRAd.


Subject(s)
Adenoviridae/physiology , Adenovirus E1 Proteins/physiology , Carcinoma, Squamous Cell/therapy , Genetic Therapy , Head and Neck Neoplasms/therapy , Oncolytic Virotherapy , TNF-Related Apoptosis-Inducing Ligand/genetics , Virus Replication , Animals , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Head and Neck Neoplasms/pathology , Humans , Male , Mice , Mice, Inbred BALB C , Xenograft Model Antitumor Assays
9.
Tumour Biol ; 31(6): 659-66, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20665144

ABSTRACT

Suberoylanilide hydroxamic acid (SAHA) is one of the most widely used histone deacetylase inhibitors. However, the potential advantage of SAHA has not been sufficiently validated as an adjunct to gene therapy of head and neck squamous cell carcinoma (HNSCC). SAHA has been shown to boost the efficiency of gene transfer by upregulating the expression of coxsackie adenoviral receptor on treated cells. The p53 family genes, p63 and p73, have been shown to have characteristics similar to p53, and although they are not confirmed as tumor suppressors, DNA-damaging signals induce their overexpression. We previously reported that the adenovirus-mediated transfer of p63 or p73 showed an effective cancer-killing effect similar to that of p53. In this study, we combined SAHA with adenoviral delivery of p63 or p73 to enhance the efficiency of gene therapy. This combination resulted in a significantly enhanced cancer-killing effect in HNSCC cell lines but had no effect on normal human fibroblasts. SAHA treatment added to ad-p63/p73 gene delivery caused an increase in p21 expression and cleaved poly-ADP ribose polymerase. Our results indicate that adjuvant SAHA treatment could be developed as a therapeutic strategy to enhance the efficiency of adenoviral gene transfer in the treatment of cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , DNA-Binding Proteins/genetics , Genetic Therapy , Head and Neck Neoplasms/drug therapy , Hydroxamic Acids/therapeutic use , Membrane Proteins/genetics , Nuclear Proteins/genetics , Tumor Suppressor Proteins/genetics , Adenoviridae/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Cyclin-Dependent Kinase Inhibitor p21/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/therapeutic use , Drug Therapy, Combination , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Luciferases/metabolism , Membrane Proteins/metabolism , Membrane Proteins/therapeutic use , Nuclear Proteins/metabolism , Nuclear Proteins/therapeutic use , Poly(ADP-ribose) Polymerases/metabolism , Receptors, Virus/metabolism , Treatment Outcome , Tumor Protein p73 , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/therapeutic use , Vorinostat
10.
Neuron ; 48(2): 267-78, 2005 Oct 20.
Article in English | MEDLINE | ID: mdl-16242407

ABSTRACT

The pigment-dispersing factor (PDF) is a neuropeptide controlling circadian behavioral rhythms in Drosophila, but its receptor is not yet known. From a large-scale temperature preference behavior screen in Drosophila, we isolated a P insertion mutant that preferred different temperatures during the day and night. This mutation, which we named han, reduced the transcript level of CG13758. We found that Han was expressed specifically in 13 pairs of circadian clock neurons in the adult brain. han null flies showed arrhythmic circadian behavior in constant darkness. The behavioral characteristics of han null mutants were similar to those of pdf null mutants. We also found that PDF binds specifically to S2 cells expressing Han, which results in the elevation of cAMP synthesis. Therefore, we herein propose that Han is a PDF receptor regulating circadian behavioral rhythm through coordination of activities of clock neurons.


Subject(s)
Circadian Rhythm/physiology , Drosophila Proteins/metabolism , Gene Expression Regulation/physiology , Neuropeptides/metabolism , Receptors, G-Protein-Coupled/metabolism , Amino Acid Sequence , Animals , Antibodies/metabolism , Behavior, Animal , Binding, Competitive , Blotting, Northern/methods , Brain/cytology , Cell Line , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Drosophila , Drosophila Proteins/genetics , Drosophila Proteins/immunology , Drosophila Proteins/physiology , Gene Expression Regulation/drug effects , Immunohistochemistry/methods , Motor Activity/physiology , Mutation , Neurons/metabolism , Periodicity , Protein Binding/physiology , RNA, Messenger/biosynthesis , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/immunology , Receptors, G-Protein-Coupled/physiology , Reverse Transcriptase Polymerase Chain Reaction/methods , Sequence Alignment , Thermosensing/genetics , Thermosensing/physiology
11.
Tumour Biol ; 29(1): 28-34, 2008.
Article in English | MEDLINE | ID: mdl-18497546

ABSTRACT

OBJECTIVE: Integrin-associated protein (CD47) binds specifically to the inhibitory receptor signal-regulatory protein. This study was designed to evaluate the role of CD47 in natural killer (NK) cell-mediated cytotoxicity against cancer cells. METHODS: Head-and-neck squamous cell carcinoma (HNSCC) cell lines were analyzed for the expression of CD47 and susceptibility to NK cell-mediated killing. Cytolytic activity was assessed by (51)Cr-specific release assays and by measuring cytokine production. RESULTS: HNSCC cell lines that had high CD47 expression showed lower levels of NK cytotoxicity than those with low CD47 expression. After pre-treating cells with neutralizing major histocompatibility complex (MHC) class I or anti-CD47 antibodies, NK cell-mediated cytotoxicity against HNSCC cell lines increased. In addition, when CD47 cDNA was transfected into Caco-2 cells, NK cell-mediated cytotoxicity decreased. CONCLUSION: These findings suggest that CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer.


Subject(s)
CD47 Antigen/immunology , Carcinoma, Squamous Cell/immunology , Head and Neck Neoplasms/immunology , Killer Cells, Natural/immunology , CD47 Antigen/genetics , Cell Line, Tumor , Cytotoxicity, Immunologic , Humans , Transfection
12.
J Microbiol ; 55(2): 147-152, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28120195

ABSTRACT

γ-Glutamyltranspeptidase (GGT) catalyzes the cleavage of γ-glutamyl compounds and the transfer of γ-glutamyl moiety to water or to amino acid/peptide acceptors. GGT can be utilized for the generation of γ-glutamyl peptides or glutamic acid, which are used as food taste enhancers. In the present study, Bacillus amyloliquefaciens SMB469 with high GGT activity was isolated from Doenjang, a traditional fermented soy food of Korea. The gene encoding GGT from B. amyloliquefaciens SMB469 (BaGGT469) was cloned from the isolate, and heterologously expressed in E. coli and B. subtilis. For comparison, three additional GGT genes were cloned from B. subtilis 168, B. licheniformis DSM 13, and B. amyloliquefaciens FZB42. The BaGGT469 protein was composed of 591 amino acids. The final protein comprises two separate polypeptide chains of 45.7 and 19.7 kDa, generated via autocatalytic cleavage. The specific activity of BaGGT469 was determined to be 17.8 U/mg with γ-L-glutamyl-p-nitroanilide as the substrate and diglycine as the acceptor. GGTs from B. amyloliquefaciens showed 1.4- and 1.7-fold higher transpeptidase activities than those from B. subtilis and B. licheniformis, respectively. Especially, recombinant B. subtilis expressing BaGGT469 demonstrated 11- and 23-fold higher GGT activity than recombinant E. coli and the native B. amyloliquefaciens, respectively, did. These results suggest that BaGGT469 can be utilized for the enzymatic production of various γ-glutamyl compounds.


Subject(s)
Bacillus amyloliquefaciens/enzymology , Bacillus amyloliquefaciens/genetics , gamma-Glutamyltransferase/genetics , gamma-Glutamyltransferase/metabolism , Amino Acid Sequence , Bacillus/enzymology , Bacillus/genetics , Bacillus amyloliquefaciens/metabolism , Cloning, Molecular , Escherichia coli/genetics , Fermentation , Glycylglycine , Molecular Weight , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Republic of Korea , Soy Foods/microbiology , Substrate Specificity , gamma-Glutamyltransferase/chemistry , gamma-Glutamyltransferase/isolation & purification
13.
Cancer Biol Ther ; 5(11): 1502-10, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17012841

ABSTRACT

p63 and p73, the p53 family proteins, are similar to p53 in many aspects: structural homology, transactivation of p53-downstream genes, and induction of apoptosis. Interestingly, they also differ from p53; in particular, they are not inhibited by viral oncoproteins such as HPV E6. This feature would be an advantage over p53 in HPV-associated cancers and therefore, we evaluated the therapeutic potentials of various p53 family proteins (p73alpha, p73beta, p63alpha and p63gamma) against HPV-infected cervical cancers. In clonogenic assay, exogenous expression of p73alpha, p73beta and p63gamma inhibited the colony formation of HPV-positive cervical cancer cells under G418- selection while p53 could not. Recombinant adenoviruses Ad/CMVp73alpha, Ad/CMVp73beta and Ad/CMVp63gamma induced potent apoptosis in all infected cervical cancers (CasKi, SiHa, HeLa, C33A, SNU682, SNU17, SNU1005, SNU703), irrespective of their HPV-infection status. Unfortunately however, Ad/CMVp73alpha, Ad/CMVp73beta, and Ad/CMVp63gamma inhibited also normal cells such as endothelial cells, fibroblasts, and keratinocytes thus, tumorspecific promoter was indispensable to the p53 family proteins-based therapy. Here we report a stringent tumor killing by p73beta in combination with ESM6, a synthetic promoter targeting the DNA tumor virusassociated cancers. Recombinant adenoviruses encoding p73beta by ESM6 (Ad/ESM6p73beta and Ad/ESM6p73bENH) expressed p73beta and induced apoptosis only in the cancer cells but not in normal cells. Collectively, we suggest that the p53 family proteins are potent therapeutic agents for HPV-associated uterine cervical cancers and ESM6 mediated expression of the p53 family proteins would be a safe and strong tumor targeting strategy.


Subject(s)
E2F1 Transcription Factor/physiology , Genes, p53 , Genetic Therapy/methods , Promoter Regions, Genetic , Adenoviridae , Cell Line , Cell Line, Tumor , Cloning, Molecular , DNA Primers , Female , Humans , Reverse Transcriptase Polymerase Chain Reaction , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/therapy
14.
Neurosci Res ; 55(4): 434-41, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16759729

ABSTRACT

In this study, we examined changes in the level and immunoreactivity of alpha-synuclein in the hippocampal CA1 region of adult (6 months old) and aged (24 months old) gerbils after 5 min of transient forebrain ischemia. The delayed neuronal death of CA1 pyramidal cells in adult gerbils was severer than that in aged gerbils 4 days after ischemia/reperfusion. Alpha-synuclein immunoreactivity in the CA1 region of adult and aged gerbils significantly changed after ischemia. In control animals, alpha-synuclein immunoreactivity and level in the aged-gerbil CA1 region were higher than those in the adult-gerbil CA1 region. In both adult and aged gerbils, alpha-synuclein immunoreactivity and level started to increase 3h after ischemia, and they were highest 1 day after ischemia. Thereafter, alpha-synuclein immunoreactivity and level decreased with time after ischemia. We also observed the effects of Cu,Zn-superoxide dismutase (SOD1) on ischemic damage using the Pep-1 transduction domain. Alpha-synuclein level in the CA1 region was lower in Pep-1-SOD1-treated adult and aged gerbils than in vehicle-treated adult and aged gerbils. We conclude that neuronal loss in the hippocampal CA1 region of adult gerbils was more prominent than that in aged gerbils 4 days after ischemia/reperfusion. The higher level of alpha-synuclein in the aged-gerbil CA1 region than that in the adult-gerbil CA1 region may be associated with the earlier induction of reactive oxygen species, and Pep-1-SOD1 potentially and reversibly inhibits the accumulation of alpha-synuclein in the CA1 region after transient ischemia.


Subject(s)
Aging/metabolism , Brain Ischemia/metabolism , Hippocampus/metabolism , Nerve Degeneration/metabolism , Superoxide Dismutase/metabolism , alpha-Synuclein/metabolism , Aging/pathology , Animals , Brain Ischemia/physiopathology , Cell Death/drug effects , Cell Death/physiology , Disease Models, Animal , Down-Regulation/drug effects , Down-Regulation/physiology , Gerbillinae , Hippocampus/pathology , Hippocampus/physiopathology , Immunohistochemistry , Male , Nerve Degeneration/etiology , Nerve Degeneration/physiopathology , Protein Structure, Tertiary/physiology , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Pyramidal Cells/pathology , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/physiopathology , Superoxide Dismutase/pharmacology , Time Factors , alpha-Synuclein/antagonists & inhibitors , alpha-Synuclein/chemistry
15.
Brain Res ; 1092(1): 214-9, 2006 May 30.
Article in English | MEDLINE | ID: mdl-16678801

ABSTRACT

In the present study, we investigated chronological changes in Cu,Zn-superoxide dismutase (SOD1) immunoreactivity and its protein levels in the hippocampal CA1 region of adult and aged gerbils after transient forebrain ischemia to compare ischemia-related changes in SOD1 in adult and aged gerbils. Delayed neuronal death in the CA1 region at 4 days after ischemic insult was prominent in adult gerbils compared to that in aged gerbils. In sham-operated gerbils, SOD1 immunoreactivity and protein level in the aged group were significantly higher than that in the adult group. At 12 h after ischemia-reperfusion, SOD1 immunoreactivity and protein level were increased in both the groups. At 1 day after ischemia, SOD1 immunoreactivity and protein level in the adult group were significantly increased: the SOD1 immunoreactivity was increased in non-pyramidal cells as well as pyramidal cells. At this time after ischemia, SOD1 immunoreactivity and protein level in the aged group were decreased: the immunoreactivity was decreased significantly in pyramidal cells. At 4 days after ischemia, SOD1 immunoreactivity was detected only in non-pyramidal cells of the CA1 region in both the groups. These results suggest that SOD1 in the gerbil hippocampal CA1 region is higher in sham-aged group than that in sham adult one, and that different changes in SOD1 in CA1 pyramidal cells after ischemia in adult and aged gerbils may indicate different processes in delayed neuronal death with time after ischemic insult.


Subject(s)
Aging/metabolism , Brain Ischemia/enzymology , Cerebral Infarction/enzymology , Hippocampus/enzymology , Reperfusion Injury/enzymology , Superoxide Dismutase/metabolism , Aging/pathology , Animals , Brain Ischemia/physiopathology , Cell Death/physiology , Cerebral Infarction/pathology , Cerebral Infarction/physiopathology , Disease Models, Animal , Gerbillinae , Hippocampus/pathology , Hippocampus/physiopathology , Immunohistochemistry , Male , Nerve Degeneration/enzymology , Nerve Degeneration/etiology , Nerve Degeneration/physiopathology , Neurons/enzymology , Neurons/pathology , Oxidative Stress/physiology , Reperfusion Injury/physiopathology , Time Factors , Up-Regulation/physiology
17.
Mycobiology ; 44(4): 217-236, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28154480

ABSTRACT

Polyporoid and corticioid fungi are among the most important wood-decay fungi. Not only do they contribute to nutrient cycling by decomposing wood debris, but they are also valuable sources for natural products. Polyporoid and corticioid wood-inhabiting fungi were investigated in Odaesan National Park. Fruit bodies were collected and identified based on morphological and molecular analyses using 28S and internal transcribed spacer regions of DNA sequences. As a result, a total of 149 species, 69 genera, 22 families, and 11 orders were recognized. Half (74 species) of the species were polypores, and the other half (75 species) were corticioid fungi. Most of the species belonged to Polyporales (92 species) followed by Hymenochaetales (33 species) and Russulales (11 species). At the genus level, a high number of species was observed from Steccherinum, Hyphodontia, Phanerochaete, Postia, and Trametes. Concerning distribution, almost all the species could be found below 1,000 m, and only 20% of the species were observed from above 1,000 m. Stereum subtomentosum, Trametes versicolor, T. hirsuta, T. pubescens, Bjerkandera adusta, and Ganoderma applanatum had wide distribution areas. Deciduous wood was the preferred substrate for the collected species. Sixty-three species were new to this region, and 21 species were new to Korea, of which 17 species were described and illustrated.

18.
Exp Mol Med ; 35(1): 23-9, 2003 Feb 28.
Article in English | MEDLINE | ID: mdl-12642900

ABSTRACT

Mammals have two major isoforms of acetyl-CoA carboxyase (ACC). The 275 kDa beta-form (ACCbeta) is predominantly in heart and skeletal muscle while the 265 kDa alpha-form (ACCalpha) is the major isoform in lipogenic tissues such as liver and adipose tissue. ACCbeta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyl-CoA transferase-1 (CPT-1), which is a rate-limiting enzyme of fatty acid oxidation in mitochondria. Previously, it was reported that MyoD and other muscle regulating factors (MRFs) up-regulate the expression of ACCbeta by interactions between these factors and several cis-elements of ACCbeta promoter. We described here that ACCbeta expression mediated by MRFs is regulated by retinoic acids. Endogenous expression of ACCbeta in differentiated H9C2 myotube was significantly increased by retinoic acid treatment. However, on transient transfection assay in H9C2 myoblast, ACCbeta promoter activity was suppressed by RXRalpha and more severely by RARalpha. These effects on ACCbeta expression in myoblasts and myotubes by RXRalpha and RARalpha seem to be mediated by their interactions with MRFs because no consensus sequence for RXRalpha and RARalpha has been found in ACCbeta promoter and retinoic acid receptors did not affect this promoter activities by itself. In transient transfection in NIH3T3 fibroblast, the activation of ACCbeta promoter by MyoD, main MRF in myoblast, was significantly suppressed by RARalpha and to a less extent by RXRalpha while the RXRalpha drastically augmented the activation by MRF4, major MRF in myotube. These results explained that retinoic acids differentially affected the action of MRFs according to their types and RXRalpha specially elevates the expression of muscle specific genes by stimulating the action of MRF4.


Subject(s)
Acetyl-CoA Carboxylase/metabolism , MyoD Protein/metabolism , Myogenic Regulatory Factors/metabolism , Receptors, Retinoic Acid/metabolism , Transcription Factors/metabolism , 3T3 Cells , Acetyl-CoA Carboxylase/genetics , Animals , Cell Differentiation , Cells, Cultured , Gene Expression Regulation, Enzymologic/drug effects , Mice , Myoblasts/drug effects , Myoblasts/metabolism , Promoter Regions, Genetic/drug effects , Receptors, Retinoic Acid/genetics , Retinoid X Receptors , Transcription Factors/genetics , Transcriptional Activation , Tretinoin/pharmacology
19.
Bioresour Technol ; 93(1): 21-8, 2004 May.
Article in English | MEDLINE | ID: mdl-14987716

ABSTRACT

The effect of food waste (FW) composted with MS (Miraculous Soil Microorganisms) was compared with commercial compost (CC) and mineral fertilizer (MF) on bacterial and fungal populations, soil enzyme activities and growth of lettuce in a greenhouse. Populations of fungi and bacteria, soil biomass, and soil enzyme activities in the rhizosphere of FW treatments significantly increased compared to control (CON), CC and MF treatments at 2, 4, and 6 weeks. The fresh weight of lettuce in FW treatments was about 2-3 times higher than that in CC at 4 and 6 week. The pH, EC, total nitrogen content, organic matter and sodium concentration in FW treatments were generally higher than those in CON, CC and MF treatments.


Subject(s)
Bacteria/enzymology , Fungi/enzymology , Lactuca/growth & development , Refuse Disposal/methods , Soil Microbiology , Soil , Biodegradation, Environmental , Food , Hydrogen-Ion Concentration , Korea , Nitrogen/metabolism , Oxidoreductases/metabolism , Phosphoric Monoester Hydrolases/metabolism , Sodium/metabolism , Time Factors
20.
J Microbiol Methods ; 97: 56-62, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24374215

ABSTRACT

White rot fungi are essential in forest ecology and are deeply involved in wood decomposition and the biodegradation of various xenobiotics. The fungal ligninolytic enzymes involved in these processes have recently become the focus of much attention for their possible biotechnological applications. Successful bioremediation requires the selection of species with desirable characteristics. In this study, 150 taxonomically and physiologically diverse white rot fungi, including 55 species, were investigated for their performance in a variety of biotechnological procedures, such as dye decolorization, gallic acid reaction, ligninolytic enzymes, and tolerance to four PAHs, phenanthrene, anthracene, fluoranthene, and pyrene. Among these fungi, six isolates showed the highest (>90%) tolerance to both individual PAH and mixed PAHs. And six isolates oxidized gallic acid with dark brown color and they rapidly decolorized RBBR within ten days. These fungi revealed various profiles when evaluated for their biotechnological performance to compare the capability of degradation of PAHs between two groups selected. As the results demonstrated the six best species selected from gallic acid more greatly degraded four PAHs than the other isolates selected via tolerance test. It provided that gallic acid reaction test can be performed to rank the fungi by their ability to degrade the PAHs. Most of all, Peniophora incarnata KUC8836 and Phlebia brevispora KUC9033 significantly degraded the four PAHs and can be considered prime candidates for the degradation of xenobiotic compounds in environmental settings.


Subject(s)
Basidiomycota/isolation & purification , Basidiomycota/metabolism , Biotechnology , Environmental Pollutants/metabolism , Polycyclic Aromatic Hydrocarbons/metabolism , Basidiomycota/drug effects , Basidiomycota/enzymology , Basidiomycota/growth & development , Biodegradation, Environmental , Polycyclic Aromatic Hydrocarbons/pharmacology , Species Specificity
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