Biomedical subjects

Chen Chen

Publications and source records attributed to Chen Chen.

150 records · Page 9Linked to original sources

PubMed2002

Is GHRH receptor essential to GHRP-2-induced GH secretion in primary cultured rat pituitary cells?

It is still controversial in rat whether the stimulation of GH secretion by GH-releasing peptides (GHRP) requires both GHRP receptor (GHRP-R) and GH-releasing hormone receptor (GHRH-R). To clarify this issue, we have postulated that inhibition of GHS-R or GHRH-R gene transcription should block GHRP-2-induced GH secretion. Rat pituitary cells were incubated for 3 days in the presence or absence of antisense 18-mer phosphorothiate oligonucleotides (ONs) complementary to the codon region of GHS-R or GHRH-R mRNAs. A significant decrease in GHRH-R and GHS-R mRNA levels was found in corresponding antisense-treated cells compared with the control cells treated with sense ON. Treatment with antisense GHS-R ON reduced (but not abolished) GHRP-2-induced GH secretion although GHRH-induced GH secretion was not altered. GHRH-stimulated GH secretion was totally abolished by the treatment with antisense GHRH-R ON, whereas GHRP-2 induced GH secretion was not affected. Treatment of cells with both GHS-R and GHRH-2 ONs however completely inhibited GHRH and GHRP-2-stimulated GH secretion. These results suggest that GHRH-R is vital for GHRH-induced GH secretion but only partially involved in GHRP-2-stimulated GH secretion under the condition of down-regulation of GHS-R gene transcription.

Animals↗

PubMed2002

The effect of two-day treatment of primary cultured ovine somatotropes with GHRP-2 on membrane voltage-gated K+ currents.

Long-term in vivo treatment with synthetic GH-releasing peptides (GHRPs) enhances the release of GH induced by endogenous GHRH. The mechanism for such an enhancement on GH release is unknown. In this experiment, somatotropes were obtained from ovine pituitaries by enzyme dissociation and enriched by density centrifugation. Membrane voltage and currents were recorded with whole-cell patch-clamp configuration. After 48-h treatment with GHRP-2 (10(-8) M), the percentage of cells with spontaneous action potential was increased (51 vs. 27%) without change of resting potential. This GHRP-2 treatment also increased the amplitude of voltage-gated K+ currents (predominantly transient A-type-like current but also delayed rectifier or K-type-like current) without modification of biophysical kinetics. Down-regulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate at the time of adding GHRP-2 blocked the increase in K+ currents. Inclusion of calphostin C (PKC inhibitor) but not H(89) (protein kinase A inhibitor) significantly reduced the increase in K+ currents by GHRP-2. Inclusion of actinomycin D (transcription inhibitor) or cycloheximide (protein synthesis inhibitor) abolished the increase in K+ currents. These data indicate that 48-h GHRP-2 treatment increases the density of K+ channels via PKC and channel protein synthesis. Such a modification on K+ channels by GHRP-2 may be partially responsible for the change of somatotrope electrophysiological properties and sensitivity to GHRH stimulation.

Animals↗

PubMed1999

Coupling of 2-Substituted 1-Fluorovinylstannanes with Organic Halides Catalyzed by Palladium(0)/Copper(I) Iodide. A Mild and Stereospecific Method to Monofluoroolefins.

The palladium-catalyzed cross-coupling reactions of (E)- or (Z)-1-fluorovinylstannanes with aryl iodides and vinyl iodides provide good yields of stereoisomerically pure substituted fluoroolefins with retention of the double bond geometry. The reaction takes place with copper(I) iodide present as a cocatalyst at ambient temperature or in refluxing tetrahydrofuran and is tolerant of a variety of functional groups. Highly functionalized and stereoisomerically pure monofluorovinyl ketones also were obtained under mild conditions by the coupling of 1-fluorovinylstannanes with acid chlorides. (1)H-{(19)F} NOE NMR experiments unequivocally established the stereochemistry of the coupling products E-14 and Z-14.

Journal Article↗

PubMedDate not supplied

Effects of molybdenum, silicon and nickel on alpha1-adrenoceptor-induced constriction of rat isolated aorta.

1. To determine the effects of trace elements on alpha1-adrenoceptor-mediated vasoconstriction, we studied the effects of molybdenum (Mo), silicon (Si) and nickel (Ni) on vasoconstrictor response to an alpha1-adrenoceptor agonist in rat aorta. 2. Cumulative concentration-contraction curves were obtained for phenylephrine (1 nmol/L-10 micromol/L) in the absence and presence of Mo, Si and Ni (0.3, 1 and 3 micromol/L) in rat aorta rings. Increasing the concentration of Mo and Si from 0.3 to 3 micromol/L shifted the cumulative concentration-contraction curve to the right, but did not reduce the maximal contractile response to phenylephrine. In contrast, Ni at 1 and 3 micromol/L shifted the cumulative concentration-contraction curve to the right and, at 3 micromol/L, reduced the maximum contractile response to phenylephrine. 3. We conclude that micromolar concentrations of Mo, Si and Ni affected alpha1-adrenoceptor-induced vasoconstriction and that Ni significantly inhibited the maximal contractile response to phenylephrine in rat isolated aorta.

Animals↗

PubMedDate not supplied

FOXO transcription factors in cell-cycle regulation and the response to oxidative stress.

Mammalian forkhead members of the class O (FOXO) transcription factors, including FOXO1, FOXO3a, and FOXO4, are implicated in the regulation of a variety of cellular processes, including the cell cycle, apoptosis, DNA repair, stress resistance, and metabolism. FOXO proteins are negatively regulated by the phosphatidylinositol 3-kinase-Akt signaling pathway, which is activated by growth factors and cytokines. Recent studies indicate that the activities of FOXO proteins are also regulated by oxidative stress, which induces their phosphorylation, translocation to the nucleus, and acetylation-deacetylation. Similar to the tumor suppressor p53, FOXO is activated by stress and induces the expression of genes that contribute to cell-cycle arrest, suggesting that it also functions as a tumor suppressor.

Animals↗

PubMedDate not supplied

Effect of reproductive hormones on ovarian epithelial tumors: II. Effect on angiogenic activity.

Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.

Allantois↗