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Biomedical subjects

Hui Zheng

Publications and source records attributed to Hui Zheng.

At least 91 records · Page 5Linked to original sources
PubMed2003

[Expression of PTEN and p27 proteins in non-Hodgkin's lymphoma].

OBJECTIVE: To investigate the effect of the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p27 proteins in non-Hodgkin's lymphoma (NHL). METHODS: The expressions of PTEN and p27 proteins were detected with immunohistochemical technique in 77 cases of NHL. RESULTS: In NHL, the positive rates of PTEN and p27 protein were 90.9% (70/77) and 51.9% (40/77), respectively. The positive strength of PTEN protein was positively correlated to that of p27 protein (r = 0.6841, P < 0.01). The expression intensity of PTEN and p27 proteins in the low grade group was all higher than that in the high grade group. The expression intensity of PTEN and p27 proteins in B NHL showed no significant difference with that of T NHL. CONCLUSION: The decrease of p27 protein expression caused by the deletion and descent of PTEN protein expression cannot effectively play the anti-oncogene role in negative regulation of the cell cycle, which makes the tumor cells more malignant.

Adolescent↗
PubMed2003

[Isolation and characterization of a novel radiation-resistant rod-shaped bacterium].

A novel radiation-resistant bacterium was isolated from soil of lake bank in Beijing. The bacterium produced orange-pigmented colonies and formed rod-shaped cells that stained gram negative alike the Deinobacter grandis previously described by Japan's scientist. It was found with electron microscopy that the isolate is of 0.6 microm - 1.6 microm size and has a 30-40 nm thickness of cell wall, being slightly larger and thicker than the Deinobacter grandis. There was a difference in the concentration and molecule weight of catalase between the isolate and the Deincoccus radiodurans R1. The deoxyribonucleic acid guanine plus cytosine (G + C) base ratio was 70.7 mol%. 16S RNA gene sequencing also showed that this rod-shaped bacterium possessed a high homology with the Deinobacter grandis, suggesting that it might be classified into the genus Deinobacter and constitute a new species in this genus.

Bacterial Proteins↗
PubMed2002

Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein.

Presenilins (PS1/PS2) play a critical role in proteolysis of beta-amyloid precursor protein (beta APP) to generate beta-amyloid, a peptide important in the pathogenesis of Alzheimer's disease. Nevertheless, several regulatory functions of PS1 have also been reported. Here we demonstrate, in neuroblastoma cells, that PS1 regulates the biogenesis of beta APP-containing vesicles from the trans-Golgi network and the endoplasmic reticulum. PS1 deficiency or the expression of loss-of-function variants leads to robust vesicle formation, concomitant with increased maturation and/or cell surface accumulation of beta APP. In contrast, release of vesicles containing beta APP is impaired in familial Alzheimer's disease (FAD)-linked PS1 mutant cells, resulting in reduced beta APP delivery to the cell surface. Moreover, diminution of surface beta APP is profound at axonal terminals in neurons expressing a PS1 FAD variant. These results suggest that PS1 regulation of beta APP trafficking may represent an alternative mechanism by which FAD-linked PS1 variants modulate beta APP processing.

Amyloid beta-Protein Precursor↗
PubMed2002

Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi.

The search for novel anxiolytics devoid of undesirable side-effects typical of classical benzodiazepines (BDZs) has been intense, and flavonoids, as a relative new class of ligands, have been shown to possess anxiolytic effects in vivo. The present study evaluated the pharmacological properties of a naturally occurring monoflavonoid, 5,7-dihydroxy-8-methoxyflavone or wogonin. The affinity (K(i)) of wogonin for the benzodiazepine site (BZD-S) on the gamma-aminobutyric acid(A) (GABA(A)) receptor complex was 0.92 microM. Using electrophysiological techniques, we showed that wogonin enhanced the GABA-activated current in rat dorsal root ganglion neurons, and in Xenopus laevis oocytes expressing recombinant rat GABA(A) receptors, the enhancement was partially reversed by the co-application of a 1 microM concentration of the BZD-S antagonist anexate (Ro15-1788). Acute toxicity and behavioral effects were examined in mice. Acute lethal activity was low, with an LD(50) of 3.9 g/kg. Oral administration of wogonin (7.5 to 30 mg/kg) elicited an anxiolytic response that was similar to that elicited by diazepam in the elevated plus-maze; a dose-dependent increase in open arm entries and time spent in open arms was observed. More importantly, its anxiolytic effect was blocked by the co-administration of Ro15-1788. In the holeboard test, not only did wogonin-treated mice experience an increased number of head-dips but they also spent more time at it, showing no signs of sedation. Furthermore, wogonin did not cause myorelaxant effects in the horizontal wire test. Taken together, these data suggest that wogonin exerts its anxiolytic effect through positive allosteric modulation of the GABA(A) receptor complex via interaction at the BZD-S. Its anxiolytic effect was not accompanied by sedative and myorelaxant side-effects typical of BDZs.

Animals↗
PubMed2002

Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis.

The Alzheimer's disease-linked gene presenilin 1 (PS1) is required for intramembrane proteolysis of APP and Notch. In addition, recent observations strongly implicate PS1 as a negative regulator of the Wnt/beta-catenin signaling pathway, although the mechanism underlying this activity is unknown. Here, we show that presenilin functions as a scaffold that rapidly couples beta-catenin phosphorylation through two sequential kinase activities independent of the Wnt-regulated Axin/CK1alpha complex. Thus, presenilin deficiency results in increased beta-catenin stability in vitro and in vivo by disconnecting the stepwise phosphorylation of beta-catenin, both in the presence and absence of Wnt stimulation. These findings highlight an aspect of beta-catenin regulation outside of the canonical Wnt-regulated pathway and a function of presenilin separate from intramembrane proteolysis.

Alzheimer Disease↗
PubMed2002

Redox properties of rubredoxin variants as a function of solvent composition and temperature: investigation of monopolar and dipolar interactions.

The role of solvent composition and temperature on equilibrium electron transfer in seven rubredoxin variants [ Clostridium pasteurianum ( Cp), V8D, V8R, V8A, V44A Cp, Pyrococcus furiosus ( Pf), and A44V Pf] were investigated to examine the role of both monopolar and dipolar interactions. The reduction potentials of all variants decreased as the polarity of the solvent decreased. The enthalpy and entropy associated with electron transfer were determined from temperature-controlled voltammetric studies. The entropic contribution [delta( Tdelta S degrees )] to the change in the reduction potential was larger for charged variants (V8D and V8R), while the enthalpic contribution [delta(-delta H degrees )] was larger for the other mutants. The large entropy change observed for monopolar variants is likely due to solvent reorganization that occurs between oxidation states. Entropic-enthalpic compensation phenomena, an observation that most proteins have an entropic term [delta( Tdelta S degrees )] and enthalpic term [delta(-delta H degrees )] with opposite signs, was observed. A correlation of the size of the amino acid side chain with delta E degrees ', delta(-delta H degrees ), and delta( Tdelta S degrees ) is also discussed.

Bacterial Proteins↗
PubMed2002

The aspartate-257 of presenilin 1 is indispensable for mouse development and production of beta-amyloid peptides through beta-catenin-independent mechanisms.

To differentiate multiple activities of presenilin 1 (PS1), we generated transgenic mice expressing two human PS1 alleles: one with the aspartate to alanine mutation at residue 257 (hPS1D257A) that impairs the proteolytic activity of PS1, and the other deleting amino acids 340-371 of the hydrophilic loop sequence (hPS1Deltacat) essential for beta-catenin interaction. We show here that although hPS1Deltacat is fully competent in rescuing the PS1-null lethal phenotype, hPS1D257A does not exhibit developmental activity. hPS1D257A also leads to the concurrent loss of the proteolytic processing of Notch and beta-amyloid precursor protein (APP) and the generation of beta-amyloid peptides (Abeta). Further, by measuring the levels of endogenous Abeta(X-40) and Abeta(X-42) in primary neuronal cultures, we confirmed the concept that PS1 is indispensable for the production of secreted Abeta.

Amyloid beta-Peptides↗
PubMed2002

Trypsin-sensitive and lipid-containing sites of the macrophage extracellular matrix bind apolipoprotein A-I and participate in ABCA1-dependent cholesterol efflux.

A unique property of the extracellular matrix of J774 and THP-1 cells has been identified, which contributes to the ability of these cells to promote cholesterol efflux. We demonstrate high level apolipoprotein (apo) A-I binding to macrophage cells (THP-1 and J774) and to their extracellular matrix (ECM). However, high level apoA-I binding is not observed on fibroblasts, HepG2 cells, or U937 cells (a macrophage cell line that does not efflux cholesterol to apoA-I or bind apoA-I on their respective ECM). Binding to the ECM of THP-1 or J774 macrophages depends on the presence of apoA-I C-terminal helices and is markedly reduced with a mutant lacking residues 187-243 (apoA-I Delta(187-243)), suggesting that the hydrophobic C terminus forms a hydrophobic interaction with the ECM. ApoA-I binding is lost upon trypsin treatment or with Triton X-100, a preparation method that de-lipidates the ECM. However, binding is recovered with re-lipidation, and is preserved with ECM prepared using cytochalasin B, which conserves the endogenous phospholipid levels of the ECM. We also demonstrate that specific cholesterol efflux to apoA-I is much reduced in cells released from their native ECM, but fully restored when ECM-depleted cells are added back to ECM in the presence of apoA-I. The apoA-I-mediated efflux is deficient in plated or suspension U937 macrophages, but is restored to high levels when the suspension U937 cells are reconstituted with the ECM of J774 cells. The ECM-dependent activity was much reduced in the presence of glyburide, indicating participation of ABCA1 (ATP-binding cassette transporter 1) in the efflux mechanism. These studies establish a novel binding site for apoA-I on the macrophage ECM that may function together with ABCA1 in promoting cholesterol efflux.

ATP Binding Cassette Transporter 1↗
PubMed2002

Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production.

The Alzheimer's disease (AD)-associated presenilin (PS) proteins are required for the gamma-secretase cleavages of the beta-amyloid precursor protein and the site 3 (S3) protease cleavage of Notch. These intramembrane cleavages release amyloid-beta peptide (Abeta), including the pathogenic 42-aa variant (Abeta(42)), as well as the beta-amyloid precursor protein and the Notch intracellular domains (AICD, NICD). Whereas Abeta is generated by endoproteolysis in the middle of the transmembrane domain, AICD and NICD are generated by cleavages at analogous positions close to the cytoplasmic border of the transmembrane domain. Numerous mutations causing familial AD (FAD) that all cause increased production of Abeta(42) have been found in the PS1 gene. Here we have investigated the previously uncharacterized, very aggressive FAD mutation L166P that causes onset of AD in adolescence. Strikingly, the PS1 L166P mutation not only induces an exceptionally high increase of Abeta(42) production but also impairs NICD production and Notch signaling, as well as AICD generation. Thus, FAD-associated PS mutants cannot only affect the generation of NICD, but also that of AICD. Moreover, further analysis with artificial L166 mutants revealed that the gamma-secretase cleavage at position 40/42 and the S3-like gamma-secretase cleavage at position 49 of the Abeta domain are both differentially affected by PS1 L166 mutants. Finally, we show that PS1 L166 mutants affect the generation of NICD and AICD in a similar manner, supporting the concept that S3 protease and S3-like gamma-secretase cleavages are mediated by identical proteolytic activities.

Alzheimer Disease↗
PubMed2002

[Relationship between the expression of PTEN protein and phosphorylation of MAPK in hepatocellular carcinomas and their surrounding liver tissues].

OBJECTIVE: To investigate the relationship between the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) protein and phosphorylation of mitogen-activated protein kinase (MAPK) in hepatocellular carcinomas (HCC) and their surrounding liver tissues. METHODS: The expression of PTEN and the phosphorylation of MAPK were detected by the SP immunohistochemical technique in 75 cases of HCC and their pericarcinomatous tissues. RESULTS: The positive rate (62.7%) and the expression intensity of PTEN in HCC were lower and weaker than those in the pericarcinomatous liver tissues (89.3%)(P < 0.01), and the expression level of PTEN was significantly related to the differentiation degree of HCC. The poorer the differentiation of HCC, the weaker the expression of PTEN protein. The positive rate (85.3%) and the expression intensity of p42/44MAPK in HCC were higher and stronger than those in the pericarcinomatous liver tissues (34.7%)(P < 0.01), and the expression intensity of p42/44MAPK was not related to the differentiation degree of HCC. A significant negative relationship was observed between the expression intensity of PTEN protein and the phosphorylation level of MAPK in HCC and their surrounding liver tissues. CONCLUSION: The decrease or deletion of PTEN protein expression may not be able to effectively inhibit the over-activation of Ras/Raf/MAPK signaling pathway, and this will result in abnormal proliferation and malignant transformation of hepatocytes in hepatocellular carcinogenesis.

Adult↗
PubMed2002

Chiral high-performance liquid chromatographic analysis of the enantiomers of XK469, a new antitumor agent, in plasma and urine.

XK469 (NSC697887), (+/-)-2-[4-(7-Chloro-2-quinoxaliny)oxy]-phenoxy propionic acid, an analog of the herbicide Assure(R), which possesses antitumor activity, especially against murine solid tumors and human xenografts, has recently been found to be the first topoisomerase II beta poison. Both R(+) and S(-) isomers are cytotoxic, although the R-isomer is more potent. A chiral high-performance liquid chromatography (HPLC) assay that utilizes Chirobiotic T column for the measurement of enantiomers of XK469 in plasma has been developed with a limit of quantitation (LOQ) of 0.2 microg/ml using a 0.2 ml plasma sample. Chloroqinoxaline sulfonamide (CQS) was used as the internal standard and the assay has been validated in rat plasma. The within-run coefficient of variations (CVs) were 5.9, 5.0, and 3.1% for the S-isomer and 8.1, 4.2, 6.4% for R(+)-XK469 at 0.2, 1, and 2 microg/ml, respectively. The between-run CVs were 10.5, 5.3, and 1.9% for S(-)- and 10.9, 6.3, and 3.6% for R(+)-XK469. Using this chiral assay, a plasma concentration time data of R(+)-,S(-)-XK469 in a Fischer 344 rat receiving i.v. dosing of S(-)XK469 at 10 mg/kg was monitored. S(-)XK469 was found to be significantly converted to the R-enantiomer in circulation even when the S-enantiomer was administered. The predominant inversion from S(-)- to R(+)-XK469 was also observed in the mouse and dog plasma. In the rat, the plasma concentration-time profiles for both isomers follow two compartmental pharmacokinetics with the t(1/2 beta) for the R-enantiomer slightly longer and the clearance of the S-enantiomer higher than the R-enantiomer.

Animals↗
PubMed2002

Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins.

Familial Alzheimer's disease-associated mutations in presenilin 1 or 2 or amyloid precursor protein result in elevated beta-amyloid, beta-amyloid accumulation, and plaque formation in the brains of affected individuals. By crossing presenilin 1 transgenic mice carrying the A246E mutation with plaque-producing amyloid precursor protein K670N/M671L transgenic mice (Tg2576), we show that co-expression of both mutant transgenes results in acceleration of amyloid accumulation and associative learning deficits. At 5 months of age with no detectable plaque pathology, amyloid precursor protein transgenic animals are impaired in contextual fear learning following two pairings of conditioned and unconditioned stimuli but appear normal following a more robust five-pairing training. At 9 months of age when beta-amyloid deposition is evident, these mice are impaired following both two-pairing and five-pairing protocols. Mice carrying both transgenes are impaired in contextual fear conditioning at either age. All transgenic animal groups performed as well as controls in cued fear conditioning, indicating that the contextual fear learning deficits are hippocampus-specific. The associative learning impairments are coincident with elevated alpha 7 nicotinic acetylcholine receptor protein in the dentate gyrus. These findings provide two robust and rapid assays for beta-amyloid-associated effects that can be performed on young animals: impaired contextual fear learning and up-regulation of alpha 7 nicotinic receptors.

Age Factors↗
PubMed2002

[Value of simultaneous determination of serum hyaluronic acid, collagen type IV and the laminin level in diagnosing liver fibrosis].

OBJECTIVE: To study the value of simultaneous determination of serum hyaluronic acid(HA), collagen Type IV (CIV) and the laminin (LN) level in the diagnosis of liver fibrosis. METHODS: Serum HA, CIV and LN were measured by ELISA in 22 healthy persons, 10 cases of acute hepatitis, 10 cases of chronic hepatitis, 10 cases of heary chronic hepatitis, and another 25 cases of posthepatitic cirrhosis. The sensitivity, specificity and accuracy of simultaneous determination were compared with those of single determination in posthepatitic cirrhosis. RESULTS: The levels of serum HA, CIV and LN in posthepatitic cirrhosis cases and heary chronic hepatitis cases were significantly higher than those in the other groups (P < 0.01). Simultaneous determination of these indices enhanced the diagnostic sensitivity, but decreased the diagnostic specificity. CONCLUSION: Simultaneous determination of HA, CIV and LN can enhance the diagnostic sensitivity. Simultaneous determination of HA and CIV is an optimal choice.

Adult↗
PubMed2002

Impairment in hippocampal long-term potentiation in mice under-expressing the Alzheimer's disease related gene presenilin-1.

Presenilin-1 (PS1) is intimately involved in cleavage of amyloid precursor protein to form beta-amyloid peptides, certain forms of which aggregate in the brains of patients with Alzheimer's disease (AD). The function(s) of PS1 and its precise involvement in the development of cognitive deficits associated with AD are unclear. We have utilised genetically modified mice that under-express PS1 (PS1(+/-) mice) to investigate the role of PS1 in hippocampal synaptic plasticity. Field excitatory postsynaptic responses elicited by baseline stimulation were indistinguishable between PS1(+/-) mice and wild-type controls. Likewise, a measure of short-term plasticity, paired-pulse facilitation, was normal in PS1(+/-) mice. However, long-term potentiation induced by multiple tetanus trains was reduced in PS1(+/-) animals. These results demonstrate that chronic reduction of PS1 activity leads to impaired synaptic plasticity, thus suggesting a role for PS1 in normal cognitive function.

Alzheimer Disease↗
PubMed2002

Peroxisome proliferator-activated receptor delta is up-regulated during vascular lesion formation and promotes post-confluent cell proliferation in vascular smooth muscle cells.

Although peroxisome proliferator-activated receptor (PPAR) delta is widely expressed in many tissues, the role of PPARdelta is poorly understood. In this study, we report that PPARdelta was up-regulated in vascular smooth muscle cells (VSMC) during vascular lesion formation. By using Northern blot analysis, we demonstrated that PPARdelta was increased by 3-4-fold in VSMC treated with platelet-derived growth factor (PDGF) (20 ng/ml). In addition, PDGF-induced PPARdelta mRNA expression neither needs de novo protein synthesis nor affects the stability of PPARdelta mRNA in VSMC. Preincubation of VSMC with phosphatidylinositol 3-kinase inhibitor (LY294002, 50 micromol/liter) or infection of VSMC with an adenovirus carrying the gene for a dominant negative form of Akt abrogated PDGF-induced PPARdelta mRNA expression, suggesting that phosphatidylinositol 3-kinase/Akt signaling pathway is involved in the regulation of PDGF-induced PPARdelta mRNA expression in VSMC. To explore the role of PPARdelta in VSMC, we generated rat vascular smooth muscle cells (A7r5) stably overexpressing PPARdelta and the control green fluorescent protein. Overexpression of PPARdelta in VSMC increased post-confluent cell proliferation by increasing the cyclin A and CDK2 as well as decreasing p57(kip2). Taken together, the results suggest that PPARdelta plays an important role in the pathology of diseases associated with VSMC proliferation, such as primary atherosclerosis and restenosis.

Animals↗
PubMed2002

Presenilins are not required for A beta 42 production in the early secretory pathway.

Presenilins 1 and 2 (PS1/PS2) have been suggested to be gamma-secretases responsible for the proteolytic cleavage of amyloid precursor protein (APP) to form amyloid-beta (A beta), a protein implicated in the development of Alzheimer's disease. Here we examined whether these presenilins are required for the generation of multiple A beta species by analyzing the production of several forms of secreted and intracellular A beta in mouse cells lacking PS1, PS2 or both proteins. Although most A beta species were abolished in PS1/PS2(-/-) cells, the production of intracellular A beta 42 generated in the endoplasmic reticulum/intermediate compartment was unaffected by the absence of these proteins, either singly or in combination. These results indicate that production of this pool of A beta occurs independently of PS1/PS2, and therefore, another gamma-secretase activity must be responsible for cleavage of APP within the early secretory compartments.

Alzheimer Disease↗
PubMed2002

Two beta-rich structural domains in GABA(A) receptor alpha(1) subunit with different physical properties: Evidence for multidomain nature of the receptor.

The type A gamma-aminobutyric acid (GABA(A)) receptor is a major inhibitory neurotransmitter-gated ion channel. Previously, we identified a membrane-proximal beta-rich (MPBR) domain in fragment C166-L296 of GABA(A) receptor alpha(1) subunit, forming nativelike pentamers. In the present study, another structural domain, the amino-terminal domain, was shown to exist in the fragment Q28-E165. The secondary structures of both fragments were beta-rich as measured using FTIR spectroscopy and estimated from the CD spectra to be 42% and 51% beta-strand for Q28-E165 and C166-L296, respectively. The CD spectrum of the combined fragment Q28-L296 was additive of the spectra of the two fragments. In addition, denaturation curves of both fragments were characteristic of cooperative transitions, supporting their domainlike nature. C166-L296 required 6.5 M of guanidine chloride for total denaturation, therefore it is extraordinarily stable, more so than Q28-E165. Moreover, effects of detergent on the molecular masses of Q28-E165 and C166-L296, as monitored using laser-scattering spectroscopy, indicated that intermolecular interactions were much more significant in C166-L296 than in Q28-E165. Effects of pH on their molecular masses suggested that ionic forces were involved in these interactions. Together the results show that the two adjacent fragments form independent folding units, MPBR and amino-terminal domains, different in secondary structure content, denaturation profile, and polymerization status, and suggest that the former may play a more important role in receptor assembly and that the extraordinary stability may underlie its intrinsic tendency to form oligomers. More significantly, the present study has provided direct evidence for the long-postulated multidomain nature of this family of receptors.

Animals↗