Biomedical subjects

Dapeng Chen

Publications and source records attributed to Dapeng Chen.

7 recordsLinked to original sources

PubMed2007

Dietary polyphenols may affect DNA methylation.

Certain dietary polyphenols, such as (-)-epigallocatechin 3-gallate (EGCG) from green tea and genistein from soybean, have been demonstrated to inhibit DNA methyltransferases (DNMT) in vitro. This inhibitory activity is associated with the demethylation of the CpG islands in the promoters and the reactivation of methylation-silenced genes such as p16INK4a, retinoic acid receptor beta, O6-methylguanine methyltransferase, human mutL homolog 1, and glutathione S-transferase-pi. These activities have been observed in human esophageal, colon, prostate, and mammary cancer cell lines, and the activity can be enhanced by the presence of histone deacetylase inhibitors or by a longer-term treatment. Many other polyphenolic compounds have lower activities in inhibiting DNMT. Catechol polyphenols may indirectly inhibit DNMT by generating S-adenosyl-L-homocysteine on their methylation by S-adenosyl-L-methionine. In theory, prevention or reversal of hypermethylation-induced inactivation of key tumor suppression genes or receptor genes by DNMT inhibitors could be an effective approach for cancer prevention. Because of the rather low bioavailability of most polyphenolic compounds, how much of an effect dietary polyphenols would have on DNA methylation in humans is not clear. The effect of normal dietary consumption of a single polyphenolic compound is probably insignificant. However, the combination of polyphenols with dietary histone deacetylase inhibitors and the additive effect of different dietary chemicals may produce some effects. On the other hand, the consumption of excessive amounts of polyphenols in dietary supplements may affect DNA methylation status. All these possibilities remain to be examined.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Expression of Nogo-A and NgR in the developing rat brain after hypoxia-ischemia.

Nogo-A and its receptor, NgR, have been shown to inhibit neurite growth in the adult rat. Therefore, we hypothesized that Nogo-A and NgR will be upregulated and thus play a similar role in the damage in developing rat brain following hypoxia-ischemia (HI). To test this hypothesis, we subjected postnatal day 7 (P7) rats to HI by permanently ligating the right common carotid artery, followed by exposure to 8%O2/92% N2 for 3 h. Rat brains at 0 h, 6 h, 12 h, 24 h and 72 h after HI, as well as from sham controls, were collected to determine histopathological damage and expression levels of Nogo-A and NgR using hematoxylin and eosin (H&E) staining, immunohistochemistry, fluorescence immunolabeling, Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). We found neuronal degeneration and edema in the ischemic cortex, becoming most prominent at 24 h following HI in this model. Accordingly, the expression of Nogo-A and NgR protein was significantly upregulated at 24 h compared with the sham controls (p<0.01). The upregulated Nogo-A and NgR immunoreactive cells were mainly located in the core of the ischemic cortex and colocalized to neurons. Meanwhile, we found the expression of both Nogo-A and NgR mRNA was increased at 6 h and peaked at 12 h in the ischemic cortex after HI, compared with sham controls. Our findings of upregulation of neurite growth inhibitor Nogo-A and its receptor NgR in ischemic cortex suggest that Nogo-A and NgR may participate in the pathology seen after HI in neonatal rats.

Analysis of Variance↗

PubMed2005

Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy.

PURPOSE: We have previously shown the reactivation of some methylation-silenced genes in cancer cells by (-)-epigallocatechin-3-gallate, the major polyphenol from green tea. To determine whether other polyphenolic compounds have similar activities, we studied the effects of soy isoflavones on DNA methylation. EXPERIMENTAL DESIGN: Enzyme assay was used to determine the inhibitory effect of genistein on DNA methyltransferase activity in nuclear extracts and purified recombinant enzyme. Methylation-specific PCR and quantitative real-time PCR were employed to examine the DNA methylation and gene expression status of retinoic acid receptor beta (RARbeta), p16INK4a, and O6-methylguanine methyltransferase (MGMT) in KYSE 510 esophageal squamous cell carcinoma cells treated with genistein alone or in combination with trichostatin, sulforaphane, or 2'-deoxy-5-aza-cytidine (5-aza-dCyd). RESULTS: Genistein (2-20 micromol/L) reversed DNA hypermethylation and reactivated RARbeta, p16INK4a, and MGMT in KYSE 510 cells. Genistein also inhibited cell growth at these concentrations. Reversal of DNA hypermethylation and reactivation of RARbeta by genistein were also observed in KYSE 150 cells and prostate cancer LNCaP and PC3 cells. Genistein (20-50 micromol/L) dose-dependently inhibited DNA methyltransferase activity, showing substrate- and methyl donor-dependent inhibition. Biochanin A and daidzein were less effective in inhibiting DNA methyltransferase activity, in reactivating RARbeta, and in inhibiting cancer cell growth. In combination with trichostatin, sulforaphane, or 5-aza-dCyd, genistein enhanced reactivation of these genes and inhibition of cell growth. CONCLUSIONS: These results indicate that genistein and related soy isoflavones reactivate methylation-silenced genes, partially through a direct inhibition of DNA methyltransferase, which may contribute to the chemopreventive activity of dietary isoflavones.

Anticarcinogenic Agents↗

PubMed2005

Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies.

(-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenol present in green tea. We previously demonstrated that EGCG was both a substrate and potent inhibitor of human liver cytosolic catechol-O-methyltransferease (COMT). We now report the structure-activity relationship for the inhibition of COMT-catalyzed O-methylation of catecholestrogens in human liver cytosol by tea catechins and some of their metabolites. The most potent inhibitors were catechins with a galloyl-type D-ring, including EGCG (IC(50)=0.07 microM), 4''-O-methyl-EGCG (IC(50)=0.10 microM), 4',4''-di-O-methyl-EGCG (4',4''-DiMeEGCG) (IC(50)=0.15 microM), and (-)-epicatechin-3-gallate (ECG) (IC(50)=0.20 microM). Catechins without the D-ring showed two to three orders of magnitude less inhibitory potency. Enzyme kinetic analyses revealed that EGCG behaved as a mixed inhibitor, whereas 4',4''-di-O-methyl-EGCG exhibited competitive kinetics for the S-adenosylmethionine (SAM), and noncompetitive kinetics for the catechol binding site. These compounds may represent a new type of COMT inhibitor. In silico molecular-modeling studies using a homology model of human COMT were conducted to aid in the understanding the catalytic and inhibitory mechanisms. Either D-ring or B-ring of EGCG could be accommodated to the substrate binding pocket of human COMT. However, the close proximity (2.6A) of 4''-OH to the critical residue Lys144, the higher acidity of the hydroxyl groups of the D-ring, and the hydrophobic interactions between the D-ring and residues in the binding pocket greatly facilitated the interaction of the D-ring with the enzyme, and resulted in increased inhibitory potency. These results provide mechanistic insight into the inhibition of COMT by commonly consumed tea catechins.

Catechin↗

PubMed2005

Benzotropolone inhibitors of estradiol methylation: kinetics and in silico modeling studies.

Natural and synthetic benzotropolone compounds were assessed in vitro for their ability to inhibit hydroxyestradiol methylation by catechol-O-methyltransferase (COMT). The compounds were also modeled in silico with a homology model of human COMT. Purpurogallin (1), purpurogallin carboxylic acid (2), and theaflavin-3,3'-digallate (6) were the most potent inhibitors of 2-hydroxy and 4-hydroxyestradiol methylation (IC(50) 0.22-0.50microM). Compounds 1 and 6 decreased the V(max) and increased the K(m) of COMT, indicating a mixed-type inhibition. Compounds 1 and 2 bound to COMT by inserting the six-membered ring of the benzotropolone into the active site. Decreased acidity of the hydroxyl groups on this ring or increased bulkiness reduced potency. Compound 6 bound by inserting the galloyl ester into the active site, which allowed the compound to overcome increased bulkiness and resulted in restored potency. Further studies are needed to determine the impact in vivo of COMT inhibition by these compounds.

Catechol O-Methyltransferase Inhibitors↗

PubMed2003

[The function of integrin beta 1 in the hypoxic cellular damage mechanism of renal tubular epithelial cell of newborn porcine].

OBJECTIVE: To inquire into the mechanism of renal deficiency in neonatal asphyxia. METHODS: The 30, 60, 90, 120 min hypoxic renal cell model was made by use of DMEM/F-12 with antimycine A. ATP content was detected by reversed-phase HPLC. The levels of integrin beta 1 of renal tubular epithelial(RTE) cell of the groups were detected using flow cytometry. RESULTS: ATP deficiency cellular model of newborn porcine RTE cell was successfully set up. The levels of ATP of the newborn porcine RET cell during 30, 60, 90, 120 min hypoxia time significantly decreased as compared with normal control (P < 0.001). The levels of integrin beta 1 of newborn porcine RTE cell decreased as the ATP deficiency time increased and the differences between the groups were statistically significant (P < 0.001). CONCLUSION: The decreased level of integrin beta 1 in the newborn porcine RTE cell during anoxia may play an important role in the newborn renal deficiency during asphyxia.

Animals↗

PubMed2002

The effects of augmented sensory feedback precision on the acquisition and retention of a simulated chiropractic task.

OBJECTIVE: To examine the effectiveness of knowledge of results precision in the acquisition and retention of a simulated manipulative procedure. DESIGN: A controlled trial was conducted, with subjects assigned to 1 of 2 interventions by means of a stratified random technique. METHODS: Seventy-one healthy male and female chiropractic student volunteers were asked to control the application of force of a simulated chiropractic manipulative procedure. Two feedback conditions (quantitative and qualitative), 2 performance conditions (light and heavy force levels), and 3 delay intervals (1, 5, and 8 days) were studied. Acquisition trials were divided into 10 blocks of 5 trials for a total of 50 trials. All subjects performed 2 blocks of 10 trials (total of 20 trials) during the no-feedback retention phase. Absolute constant error (/CE/) was analyzed as the measure of performance accuracy, and variable error (VE) was used to determine performance consistency. RESULTS: No significant main effect for the 2 feedback groups was found for /CE/ and VE during the acquisition phase. A significant main effect for force was found for /CE/ and VE, indicating that subjects were more accurate during light conditions than heavy conditions. There was a significant main effect for trial blocks for both /CE/ and VE, indicating that groups became more accurate and consistent as a result of practice. During the retention phase, a significant main effect for retention group conditions was identified for /CE/ but not for VE. This indicates that the retention groups differed in accuracy but were similar in consistency. Post hoc analyses indicated that subjects were less accurate as time between acquisition and retention trials increased. There was a significant main effect for trial blocks for VE but not for /CE/, suggesting that groups became more consistent between trial blocks. A significant group trial block interaction was revealed for /CE/. No other main effects or interactions in the analyses were significant for /CE/ or VE. CONCLUSION: The findings of this study suggest that practice sessions with kinetic devices (simulators) and performance feedback, whether quantitative or qualitative, may be useful when implemented to assist the performance of complex motor skills. There is not enough evidence to support the idea that the training used in this study could generate lasting learning effects.

Adult↗