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Heo H.-S.,Pusan National University | Heo H.-S.,Molecular Inflammation Research Center for Aging Intervention | Lee S.,Ewha Womans University | Kim J.M.,Molecular Inflammation Research Center for Aging Intervention | And 2 more authors.
Biochemical and Biophysical Research Communications

Peptide mass fingerprinting (PMF) has become one of the most widely used methods for rapid identification of proteins in proteomics research. Many peaks, however, remain unassigned after PMF analysis, partly because of post-translational modification and the limited scope of protein sequences. Almost all PMF tools employ only known or predicted protein sequences and do not include open reading frames (ORFs) in the genome, which eliminates the chance of finding novel functional peptides. Unlike most tools that search protein sequences from known coding sequences, the tool we developed uses a database for theoretical small ORFs (tsORFs) and a PMF application using a tsORFs database (tsORFdb). The tsORFdb is a database for ORFeome that encompasses all potential tsORFs derived from whole genome sequences as well as the predicted ones. The massProphet system tries to extend the search scope to include the ORFeome using the tsORFdb. The tsORFdb and massProphet should be useful for proteomics research to give information about unknown small ORFs as well as predicted and registered proteins. © 2010 Elsevier Inc. All rights reserved. Source

Hwang S.Y.,Pusan National University | Kang Y.J.,Pusan National University | Sung B.,Pusan National University | Kim M.,Pusan National University | And 7 more authors.
International Journal of Molecular Medicine

Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors, folic acid is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness and difficulty in walking. Previous studies have indicated that folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of folic acid on neo-myotube maturation and differentiation using C2C12 murine myoblasts. We found that folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated myotubes during myogenic differentiation. Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway. Source

Heo H.-S.,Molecular Inflammation Research Center for Aging Intervention | Heo H.-S.,Pusan National University | Kim J.M.,Molecular Inflammation Research Center for Aging Intervention | Kim H.S.,Molecular Inflammation Research Center for Aging Intervention | And 3 more authors.
Biochemical and Biophysical Research Communications

Predicting and assigning functions for putative genes and hypothetical proteins are important goals in the post-genomic era. Many methods have been developed for this challenge, among which the straightforward way is function prediction using sequence homology. Homology-based function prediction applies sequence-alignment tools to find homology relationships between functions of known genes and putative genes, and transfers the most similar functions of known genes to putative genes. This approach fails completely for about 30% of genes, and only 3% have any supporting experimental evidence. According to supporting evidence, genes are known to be regulated by a common transcriptional regulatory element if the expression profiles of the coregulated genes are highly correlated. We propose a new conceptual approach and method for nonhomology-based function-prediction methods for putative genes and hypothetical proteins. We have established patterns, also considered to be combinations, of common transcriptional regulatory elements for functional classes of mouse (Mus musculus) transcripts (the TREP_DB). Using these results, we have also established a function-prediction method for putative genes and hypothetical proteins. © 2010 Elsevier Inc. Source

Kim J.M.,Molecular Inflammation Research Center for Aging Intervention | Lee E.K.,Molecular Inflammation Research Center for Aging Intervention | Park G.,University of New Hampshire | Kim M.K.,Pusan National University | And 4 more authors.
Free Radical Research

Morin is a flavone that has anti-inflammatory effects through a mechanism that is not well understood. Based on the extreme sensitive nature of the transcription factor, NF-kB to redox change, it is postulated that morin's anti-NF-κB activation likely depends on its ability to scavenge excessive reactive species [RS]. The present study assessed the extent of morin's ability to modulate RS-induced NF-κB activation through its scavenging activity. Results indicate that morin neutralized RS in vitro and inhibited t-BHP-induced RS generation. It also examined morin for suppressed redox-sensitive transcription factor NF-κB activation via reduced DNA binding activity, IκBα phosphorylation and p65/p50 nuclear translocation. The more important finding was that suppression of the NF-κB cascade by morin was modulated through the ERK and p38 MAPKs signal transduction pathways in endothelial cells. As a consequence, morin's anti-oxidant effect extended expression level of NF-κB dependent pro-inflammatory genes, thereby reducing COX-2, iNOS and 5-LOX. The data indicate that morin has strong anti-oxidative power against RS-induced NF-κB modulation through the ERK and p38 MAPKs signalling pathways by its RS scavenging activity. The significance of the current study is the new revelation that morin may have potential as an effective anti-inflammatory therapeutic agent. © 2010 Informa UK Ltd. Source

Kim D.H.,Molecular Inflammation Research Center for Aging Intervention | Sung B.,Molecular Inflammation Research Center for Aging Intervention | Kang Y.J.,Molecular Inflammation Research Center for Aging Intervention | Jang J.Y.,Molecular Inflammation Research Center for Aging Intervention | And 9 more authors.
International Journal of Oncology

Betaine is an important human nutrient obtained from various foods and studies in animals and humans have provided results suggesting their pathogenesis of various chronic diseases and points to a role in risk assessment and disease prevention. However, the molecular mechanisms of its activity remain poorly understood and warrant further investigation. This study was performed to investigate the anti-inflammation and tumor preventing capacity of betaine on colitis-associated cancer in mice. In in vivo experiments, we induced colon tumors in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS) and evaluated the effects of betaine on tumor growth. Administration with betaine significantly decreased the incidence of tumor formation with downregulation of inflammation. Treatment with betaine inhibited ROS generation and GSSG concentration in colonic mucosa. Based on the qPCR data, administration of betaine inhibited inflammatory cytokines such TNF-α, IL-6, iNOS and COX-2. In in vitro experiments, LPS-induced NF-κB and inflammatory-related cytokines were inhibited by betaine treatment in RAW 264.7 murine macrophage cells. Our findings suggest that betaine is one of the candidates for the prevention of inflammation-associated colon carcinogenesis. Source

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