KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during myoblast differentiation.

Transcription factor SOX4 has been implicated in skeletal myoblast differentiation through the regulation of Cald1 gene expression; however, the detailed molecular mechanism underlying this process is largely unknown. Here, we demonstrate that SOX4 acetylation at lysine 95 by KAT5 (also known as Tip60) is essential for Cald1 promoter activity at the onset of C2C12 myoblast differentiation. KAT5 chromodomain was found to facilitate SOX4 recruitment to the Cald1 promoter, which is involved in chromatin remodeling at the promoter. Chromatin occupancy analysis of SOX4, KAT5, and HDAC1 indicated that the expression of putative SOX4 target genes during C2C12 myoblast differentiation is specifically regulated by the molecular switching of the co-activator KAT5 and the co-repressor HDAC1 on SOX4 transcriptional activation.

PrPc is temporospatially expressed in molar development of rats.

Odontogenesis, tooth development, is derived from two tissue components: ectoderm and neural crest-derived mesenchyme. Cyto-differentiation of odontogenic cells during development involves time-dependent and sequential regulation of genetic programs. This study was conducted to detect molecules implicated in cyto-differentiation of developing molar germs of rats. Differential display-PCR revealed that PrP(c) was differentially expressed between cap/early bell-staged germs (maxillary 3rd molar germs) and root formation-staged germs (maxillary 2nd molar germs) at postnatal day 9. Both levels of PrP(c) mRNA and protein expression were higher in the root formation stage than the cap/early bell stage and increased in a time-dependent manner. Immunofluorescence revealed for the first time that PrP(c) was not localized in the enamel organ, but localized in dental follicular cells for the development of the periodontal ligament and cementum as well as odontoblasts, both of which are of neural crest origin. These results suggest that the physiological functions of the PrP(c) in tooth development may be implicated in the differentiation of neural crest-derived mesenchyme including the periodontal tissues for root formation rather than epithelial tissue.

Diffusion tensor imaging of normal prostate at 3 T: effect of number of diffusion-encoding directions on quantitation and image quality.

OBJECTIVE: The purpose of this study was to prospectively investigate differences of diffusion tensor imaging (DTI) using a different number of diffusion-encoding directions and to evaluate the feasibility of tractography in healthy prostate at 3 T. METHOD: 12 healthy volunteers underwent DTI with single-shot echo-planar imaging at 3 T using a phased-array coil. Diffusion gradients of each DTI were applied in 6 (Group 1), 15 (Group 2) and 32 (Group 3) non-collinear directions. For each group, the mean apparent diffusion coefficient (ADC), fractional anisotrophy (FA) and signal-to-noise ratio (SNR) were measured in the peripheral zone (PZ) and central gland (CG). The quality of diffusion-weighted and tractographic images were also evaluated. RESULTS: In all three groups, the mean ADC value of the CG was statistically lower than that of the PZ (p<0.01) and the mean FA value of the CG was statistically greater than that of the PZ (p<0.01). For the mean FA value of the CG, no statistical difference was seen among the three groups (p=0.052). However, the mean FA value of the PZ showed a statistical difference among the three groups (p=0.035). No significant difference in SNR values was seen among the three groups (p>0.05). Imaging quality of diffusion-weighted tractographic images was rated as satisfactory or better in all three groups and was similar among the three groups. CONCLUSION: In conclusion, prostate DTI at 3 T was feasible with different numbers of diffusion-encoding directions. The number of diffusion-encoding directions did not have a significant effect on imaging quality.

Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1-PUMA pathway.

DPC4 (deleted in pancreatic cancer 4)/Smad4 is an essential factor in transforming growth factor (TGF)-ß signaling and is also known as a frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-ß can contribute to cancer progression through transcriptional target genes, such as Snail, MMPs, and epithelial-mesenchymal transition (EMT)-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-ß signaling-independent advantage, which should be essential for cancer cell survival. Here, we provide the evidences about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4-deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that Siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues not only show the elevated expression of PAK1, but also support our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 renders the resistance to serum-deprivation-induced cell death, which is the TGF-ß-independent tumor suppressive role of Smad4.

The relationship between body mass index and the prevalence of obesity-related diseases based on the 1995 National Health Interview Survey in Korea.

This study estimated the body mass index (BMI) distribution of Koreans and examined the relationship between BMI and obesity-related diseases, in particular hypertension and diabetes mellitus. We also attempted to provide primary data to determine suitable BMI cut-off points for obesity in Korea. The 1995 National Health Interview Study (NHIS) data were used to estimate BMI and the prevalence of hypertension and diabetes mellitus. A random sample of 5750 Koreans (15-69 years of age) were investigated. BMI was calculated by self-reported weights and heights. The diagnoses of hypertension and diabetes mellitus were obtained from self-reported conditions specified in response to consultations with physicians. The mean BMI was 22.6+/-2.6 kg m(-2) for males and 21.7+/-4.8 kg m(-2) for females. The prevalence of hypertension and diabetes mellitus increased with BMI. The odds ratios of the third quartile of BMI (21.9-23.8 kg m(-2)) for hypertension and diabetes mellitus compared with the first quartile were 6.04 and 3.22, respectively. The odds ratio of the fourth quartile (>23.8 kg m(-2)) of BMI was not significantly different from that of the third quartile. The risk of hypertension and diabetes mellitus increased at the third quartile of BMI (21.9-23.8 kg m(-2)), this quartile being much lower than both the current World Health Organization (WHO) BMI cut-off point of overweight of 25.0 kg m(-2), and the 90th percentile proposed in the Monica project, BMI 26.4 kg m(-2). This finding was notable considering the fact that both hypertension and diabetes mellitus occur in Koreans with lower BMIs than whites. Further studies are necessary to identify the BMI cut-off point for obesity in Korea.

Cloning and characterization of a hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase induced in response to UV-C and wounding from Capsicum annuum.

Hydroxycinnamoyl-CoA : tyramine N-(hydroxycinnamoyl) transferase (THT) is a pivotal enzyme in the synthesis of N-(hydroxycinnamoyl)-amines, which are associated with cell wall fortification in plants. The cDNA encoding THT was cloned from the leaves of UV-C treated Capsicum annuum (hot pepper) using a differential screening strategy. The predicted protein encoded by the THT cDNA is 250 amino acids in length and has a relative molecular mass of 28,221. The protein sequence derived from the cDNA shares 76% and 67% identity with the potato and tobacco THT protein sequences, respectively. The recombinant pepper THT enzyme was purified using a bacterial overexpression system. The purified enzyme has a broad substrate specificity including acyl donors such as cinnamoyl-, sinapoyl-, feruloyl-, caffeoyl-, and 4-coumaroyl-CoA and acceptors such as tyramine and octopamine. In UV-C treated plants, the THT mRNA was strongly induced in leaves, and the elevated level of expression was stable for up to 36 h. THT mRNA also increased in leaves that were detached from the plant but not treated with UV-C. THT expression was measured in different plant tissues, and was constitutive at a similar level in leaf, root, stem, flower and fruit. Induction of THT mRNA was correlated with an increase in THT protein.

Magnesium inhibits nickel-induced genotoxicity and formation of reactive oxygen.

Nickel compounds are recognized to cause nasal and lung cancers. Magnesium is an effective protector against nickel-induced carcinogenesis in vivo, although its mechanisms of protection remain elusive. The effects of magnesium carbonate on the cytotoxicity and genotoxicity induced by nickel subsulfide were examined with respect to the inhibition of cell proliferation, micronuclei formation, DNA-protein cross-link formation, and intranuclear nickel concentration. The generation of reactive oxygen by nickel chloride was also analyzed by observing 8-hydroxy-deoxyguanosine formation from deoxyguanosine in the presence and absence of magnesium chloride. The suppression of up to 64% of the proliferation of BALB/3T3 fibroblasts by nickel subsulfide (1 microgram/ml) was reversed by magnesium. The nickel compound increased not only the number of micronuclei but also the amount of DNA-protein cross-links examined with CHO and BALB/3T3 cells, respectively. These genotoxic effects of nickel were again lessened by magnesium carbonate. In addition, the cellular accumulation of nickel increased 80-fold with nickel subsulfide treatment and decreased with magnesium carbonate treatment. Nickel also enhanced 8-hydroxy-deoxyguanosine formation in the presence of H2O2 and ascorbic acid, where magnesium played another suppressive role. In fact, inhibition by magnesium was still observed even in the absence of nickel treatment. These results suggest that the protective role of magnesium in nickel-induced cytotoxicity and genotoxicity can be attributed to its ability to reduce either the intracellular nickel concentration or reactive oxygen formation.