Selenoprotein W promotes cell cycle recovery from G2 arrest through the activation of CDC25B

AbstractSelenoprotein W (SelW) contains a highly reactive selenocysteine (Sec; U) in the CXXU motif corresponding to the CXXC motif in thioredoxin (Trx) and thus it appears to be involved in regulating the cellular redox state. Recent reports on the interaction between SelW and 14-3-3 suggest that SelW may be redox dependently involved in the cell cycle. However, the precise function of SelW has not yet been elucidated. Here, we show that SelW is involved in the G2–M transition, especially in the recovery from G2 arrest after deoxyribonucleic acid (DNA) damage. Knockdown of SelW significantly accumulated phosphorylated cyclin‐dependent kinase (Cdk1), which eventually led to a delay in recovery from G2 arrest. We also found that inactive Cdk1 is caused by the sustained inactivation of CDC25B, which removes the inhibitory phosphate from Cdk1. Our observation from this study reveals that SelW activated CDC25B by promoting the dissociation of 14-3-3 from CDC25B through the reduction of the intramolecular disulfide bond during recovery. We suggest that SelW plays an important role in the recovery from G2 arrest by determining the dissociation of 14-3-3 from CDC25B in a redox-dependent manner

A Case of Streptococcus gallolyticus subsp gallolyticus Infective Endocarditis with Colon Cancer: Identification by 16S Ribosomal DNA Sequencing

Although the association between Streptococcus bovis endocarditis and colon carcinoma is well known, very few cases of S. bovis infection associated with underlying malignancies have been reported in Korea The S. bovis group has been recently reclassified and renamed as Streptococcus gallolyticus and Streptococcus infantarius subspecies under a new nomenclature system. We report a case of infective endocarditis with colon cancer caused by S. gallolyticus subsp. gallolyticus (previously named S. bovis biotype 1). A 59-yr-old woman presented with a 1-month history of fever. Initial blood cultures were positive for gram-positive cocci, and echocardiography showed vegetation on mitral and aortic valves. Antibiotic treatment for infective endocarditis was started. The infecting strain was a catalase-negative and bile-esculin-positive alpha-hemolytic Streptococcus susceptible to penicillin and vancomycin. The strain was identified as S. gallolyticus subsp. gallolyticus with the use of the Vitek 2 GPI and API 20 Strep systems (bioMerieux, USA). The 16S rDNA sequences of the blood culture isolates showed 100% homology with those of S. gallolyticus subsp. gallolyticus reported in GenBank. The identification of the infecting organism, and the subsequent communication among clinical microbiologists and physicians about the changed nomenclature, led to the detection of colon cancer. The patient recovered after treatment with antibiotics, valve surgery, and operation for colon cancer. This is the first report of biochemical and genetic identification of S. gallolyticus subsp. gallolyticus causing infective endocarditis associated with underlying colon cancer in a Korean patient. (Korean J Lib Med 2010;30:160-5)Herrero IA, 2002, J CLIN MICROBIOL, V40, P3848, DOI 10.1128/JCM.40.10.3848-3850.2002Beck M, 2008, J CLIN MICROBIOL, V46, P2966, DOI 10.1128/JCM.00078-08Poyart C, 2002, INT J SYST EVOL MICR, V52, P1247, DOI 10.1099/js.0.02044-0Clarridge JE, 2001, J CLIN MICROBIOL, V39, P1549KOH DW, 2001, KOREAN J GASTROINTES, V23, P503Schlegel L, 2000, INT J SYST EVOL MICR, V50, P1425Ellmerich S, 2000, CARCINOGENESIS, V21, P753KWACK KK, 2000, KOREAN J MED, V59, P198Devriese LA, 1998, J CLIN MICROBIOL, V36, P3520COYKENDALL AL, 1989, CLIN MICROBIOL REV, V2, P315Schlegel L, 2003, INT J SYST EVOL MICR, V53, P631, DOI 10.1099/ijs.0.02361-0UH Y, 2006, KOREAN J CLIN MICROB, V9, P36RUOFF KL, 1989, J CLIN MICROBIOL, V27, P305FARROW JAE, 1984, SYST APPL MICROBIOL, V5, P467WILSON WR, 1981, JAMA-J AM MED ASSOC, V245, P360KLEIN RS, 1979, ANN INTERN MED, V91, P560KLEIN RS, 1977, NEW ENGL J MED, V297, P800MC CW, 1951, J MED ASS STATE ALA, V21, P162

Transcription Factor Sp1 Is Involved in Expressional Regulation of Coxsackie and Adenovirus Receptor in Cancer Cells

Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (−503/−498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression

Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells

A DNA tetrahedron is employed for efficient delivery of doxorubicin into drug-resistant breast cancer cells. The drug delivered with the DNA nanoconstruct is considerably cytotoxic, whereas free doxorubicin is virtually non-cytotoxic for the drug-resistant cells. Thus, the DNA tetrahedron, made of the inherently natural and biocompatible material, can be a good candidate for the drug carrier to overcome MDR in cancer cells.close11

Effect of 660 nm Light-Emitting Diode on the Wound Healing in Fibroblast-Like Cell Lines

Light in the red to near-infrared (NIR) range (630–1000 nm), which is generated using low energy laser or light-emitting diode (LED) arrays, was reported to have a range of beneficial biological effects in many injury models. NIR via a LED is a well-accepted therapeutic tool for the treatment of infected, ischemic, and hypoxic wounds as well as other soft tissue injuries in humans and animals. This study examined the effects of exposure to 660 nm red LED light at intensities of 2.5, 5.5, and 8.5 mW/cm2 for 5, 10, and 20 min on wound healing and proliferation in fibroblast-like cells, such as L929 mouse fibroblasts and human gingival fibroblasts (HGF-1). A photo illumination-cell culture system was designed to evaluate the cell proliferation and wound healing of fibroblast-like cells exposed to 600 nm LED light. The cell proliferation was evaluated by MTT assay, and a scratched wound assay was performed to assess the rate of migrating cells and the healing effect. Exposure to the 660 nm red LED resulted in an increase in cell proliferation and migration compared to the control, indicating its potential use as a phototherapeutic agent

Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein

AbstractSelenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3

Genome-wide genetic aberrations of thymoma using cDNA microarray based comparative genomic hybridization

BACKGROUND: Thymoma is a heterogeneous group of tumors in biology and clinical behavior. Even though thymoma is divided into five subgroups following the World Health Organization classification, the nature of the disease is mixed within the subgroups. RESULTS: We investigated the molecular characteristics of genetic changes variation of thymoma using cDNA microarray based-comparative genomic hybridization (CGH) with a 17 K cDNA microarray in an indirect, sex-matched design. Genomic DNA from the paraffin embedded 39 thymoma tissues (A 6, AB 11, B1 7, B2 7, B3 8) labeled with Cy-3 was co-hybridized with the reference placenta gDNA labeled with Cy-5. Using the CAMVS software, we investigated the deletions on chromosomes 1, 2, 3, 4, 5, 6, 8, 12, 13 and 18 throughout the thymoma. Then, we evaluated the genetic variations of thymoma based on the subgroups and the clinical behavior. First, the 36 significant genes differentiating five subgroups were selected by Significance Analysis of Microarray. Based on these genes, type AB was suggested to be heterogeneous at the molecular level as well as histologically. Next, we observed that the thymoma was divided into A, B (1, 2) and B3 subgroups with 33 significant genes. In addition, we selected 70 genes differentiating types A and B3, which differ largely in clinical behaviors. Finally, the 11 heterogeneous AB subtypes were able to correctly assign into A and B (1, 2) types based on their genetic characteristics. CONCLUSION: In our study, we observed the genome-wide chromosomal aberrations of thymoma and identified significant gene sets with genetic variations related to thymoma subgroups, which might provide useful information for thymoma pathobiology.ope

Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes

Cathepsin B and matrix metalloproteinase (MMP) play key roles in tumor progression by controlled degradation of extracellular matrix. Consequently, these proteases have been attracted in cancer research, and many imaging probes utilizing these proteases have been developed. Our groups developed cathepsin B and MMP imaging nanoprobes based on polymer nanoparticle platform. Both cathepsin B and MMP imaging probes used near-infrared fluorescence (NIRF) dye and dark-quencher to for high sensitivity, and protease-sensitive peptide sequence in each probe authorized high specificity of the probes. We compared the bioactivities of cathepsin B and MMP sensitive probes in cancer-related environments to investigate the biological property of the probes. As a result, cathepsin B probe showed fluorescence recovery after the probe entered the cytoplasm. This property could be useful to evaluate the cytoplasmic targeted delivery by using probe-conjugated nanoparticles in vivo. On the other hand, MMP probe was superior in specificity in vivo and tissue study. This comparative study will provide precise information about peptide-based optical probes, and allow their proper application to cancer diagnosis