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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 19 recordsLinked to original sources
PubMed2001

Unexpected transcriptional induction of monocyte chemoattractant protein 1 by proteasome inhibition: involvement of the c-Jun N-terminal kinase-activator protein 1 pathway.

Proteasome inhibitors, the well-known inhibitors of NF-kappaB, are recently considered therapeutic agents for inflammation. However, the anti-inflammatory properties of these agents have not been fully evaluated. In this report we describe a novel effect of proteasome inhibitors on the expression of monocyte chemoattractant protein 1 (MCP-1) in mesangial cells. We found that proteasome inhibitor MG132 dose-dependently induced expression of MCP-1 at the transcriptional level. The stimulatory effect was similarly observed with other proteasome inhibitors (proteasome inhibitor 1 and lactacystin) and in other cell types (NRK fibroblasts). The 5'-flanking region of the MCP-1 gene contains multiple AP-1 sites. To explore the mechanisms involved, we examined the effects of proteasome inhibition on the AP-1 pathway. Northern blot analysis showed that MG132 rapidly induced the expression of c-jun, but not c-fos. Immunoblot analysis showed that MG132 prevented degradation of c-Jun protein. Kinase assay revealed that c-Jun N-terminal kinase (JNK) was rapidly activated by MG132. Consistent with these results, a reporter assay showed that AP-1 activity was up-regulated after treatment with MG132. Curcumin, a pharmacological inhibitor of the JNK-AP-1 pathway, abrogated the induction of MCP-1 by MG132. Similarly, stable transfection with a dominant-negative mutant of c-Jun attenuated both MG132-induced activation of AP-1 and expression of MCP-1. The transcriptional activation by proteasome inhibitors was observed not only in MCP-1, but also in other AP-1-dependent genes, including stromelysin and mitogen-activated protein kinase phosphatase 1. These data revealed that proteasome inhibition triggered the expression of MCP-1 and other genes via the multistep induction of the JNK-c-Jun/AP-1 pathway.

Animals↗
PubMed2001

Rhenium oxo complexes of a chelating diyne ligand. Synthesis and study of the kinetics of protonation.

A series of oxo complexes, Re(O)X(diyne) (X = I, Me, Et), have been prepared from 2,7-nonadiyne and Re(O)I(3)(PPh(3))(2). Addition of B(C(6)F(5))(3) to Re(O)I(2,7-nonadiyne) (5) results in coordination of the oxo ligand to the boron. The protonation of Re(O)(X)(2-butyne)(2) and Re(O)(X)(2,7-nonadiyne)(2) with a variety of acids has been examined. With 5 and HBF(4)/Et(2)O, the ultimate product was [Re(CH(3)CN)(3)(I)(2,7-nonadiyne)](2+) (7). The conversion of 5 to 7 changes the conformation of the diyne ligand from a "chair" to a "boat" and shifts its propargylic protons considerably downfield in the (1)H NMR. The kinetics of the protonation of Re(O)I(2,7-nonadiyne) (5) by CF(3)SO(3)H in CH(3)CN have been monitored by visible spectroscopy, in a stopped-flow apparatus, and by low temperature (1)H NMR. Two second-order rate constants, presumably successive protonations, were observed in the stopped-flow, k(1) = 11.9 M(-)(1) s(-)(1) and k(2) = 3.8 M(-)(1) s(-)(1). Low temperature (1)H NMR spectroscopy indicated that the resulting solution contained a mixture of two doubly protonated intermediates X and Y, each of which slowly formed the product 7 via an acid-independent process.

Journal Article↗
PubMed2001

The distribution patterns of trace elements in the brain and erythrocytes in a rat experimental model of iodine deficiency.

Cretinism is a disease characterized by neurological defects associated with severe iodine deficiency. In a rat model of severe iodine deficiency, we investigated the distribution pattern of trace elements (iodine [I], selenium [Se], and bromine [Br] in brain tissue samples; potassium [K], calcium [Ca], manganese [Mn], iron [Fe], copper [Cu], zinc [Zn], rubidium [Rb], and lead [Pb] in erythrocytes) after supplementing the rats with I and/or Se. Neutron activation analysis, proton induced x-ray emission and x-ray fluorescence were used. The serum levels of total and free thyroxine (T4, FT4), and of total, free, and reverse triiodothyronine (T3, FT3, rT3, respectively) were assessed by radioimmunoassay. The results were statistically evaluated by one-way analysis of variance and bivariate correlation. The study indicated that the levels of T4, FT4, and rT3 increased in the serum of iodine-deficient rats supplemented with I or I + Se. In the same animals, we documented alterations of the content of Br in the brain, and of Zn, Mn, Cu, and Rb in erythrocytes, whereas the brain content of I and Se was unchanged. Thus, I and I + Se supplementation improves thyroid hormone metabolism but affects the content of selected trace elements in erythrocytes and of Br in the brain. The data stimulate further clarification of the role of trace elements in the central nervous system.

Animals↗
PubMed2001

Miniaturized amperometric biosensor based on xanthine oxidase for monitoring hypoxanthine in cell culture media.

Fabrication and characterization of miniaturized amperometric hypoxanthine biosensors are described and demonstrated for monitoring hypoxanthine in myocardial cell culture media. The sensors are based on xanthine oxidase (XO) immobilized on carbon fiber microelectrodes (CFMEs) using a composite film of Nafion and electropolymerized phenol (PPh). Nafion was used for XO immobilization because of its film hydrophobicity, enzyme-favored environment, and electrostatic interaction with XO, which was dispersed in Nafion film by immersing the Nafion-coated CFMEs in XO solution for 5 h. PPh film was formed as an overlay on Nafion and XO-modified CFMEs via electropolymerization. Hypoxanthine was measured with the sensor by the oxidation of enzymatic reaction products, hydrogen peroxide (H(2)O(2)), and uric acid (UA) at +0.60 V (vs Ag/AgCl). The use of Nafion and PPh as a matrix for XO immobilization yields enhanced specificity, sensitivity, and linearity toward hypoxanthine. A dynamic linear range of 5.0 microM to 1.8 mM was achieved with a calculated detection limit of 1.5 microM (S/N = 3) and a sensitivity of 3.144 nA/mM. In addition, the measurement was virtually interference-free from easily oxidizable species such as UA, ascorbic acid, physiological levels of neurotransmitters, and their principal metabolites. The biosensor was used to monitor hypoxanthine accumulation in myocardial cell culture media, in which the level of extracellular hypoxanthine was found to increase with ischemic tolerance.

Animals↗
PubMed2001

Probing local conformational changes during equilibrium unfolding of firefly luciferase: fluorescence and circular dichroism studies of single tryptophan mutants.

Firefly luciferase is a monomeric protein composed of two globular domains. There is a wide cleft between the two domains. The N-terminal domain can be further divided into A-, B-, and C-subdomains. Previous studies showed that in vitro unfolding of firefly luciferase induced by guanidinium chloride can be described as a four-state equilibrium with two inactive intermediates (Herbst, R., et al. (1997) J. Biol. Chem. 272, 7099-7105). In order to monitor spectroscopically the conformational changes that occur in the different domains and subdomains during the multi-state unfolding process, we constructed a series of single-tryptophan mutants. These mutants were purified and characterized and shown to retain essentially all of the structural properties of the wild-type luciferase. Under equilibrium conditions, the unfolding of each mutant protein were studied by means of fluorescence and circular dichroism. The results show that different conformational changes occur in specific regions, suggesting a sequential unfolding process for firefly luciferase. Under 2.5 M GdmCl, whereas the N-domain unfolds partially holding half of the secondary structure content, the C-domain unfolds almost completely. In the equilibrium intermediate I(2), the secondary structure might stem mostly from the A- and B- subdomains.

Animals↗
PubMed2001

Trapping conformational intermediate states in the reaction center protein from photosynthetic bacteria.

In protein, conformational changes are often crucial for function but not easy to observe. Two functionally relevant conformational intermediate states of photosynthetic reaction center protein (RCs) are trapped and characterized at low temperature. RCs frozen in the dark do not allow electron transfer from the reduced primary quinone, Q(A)(-), to the secondary quinone, Q(B). In contrast, RCs frozen under illumination in the product (P(+)Q(A)Q(B)(-)) state, with the oxidized electron donor, P(+), and reduced Q(B)(-), return to the ground state at cryogenic temperature in a conformation that allows a high yield of Q(B) reduction. Thus, RCs frozen under illumination are found to be trapped above the ground state in a conformation that allows product formation. When the temperature is raised above 120 K, the protein relaxes to an inactive conformation which is different from the RCs frozen in the dark. The activation energy for this change is 87 +/- 8 meV, and the active and inactive states differ in energy by only 16 +/- 3 meV. Thus, there are several conformational substates along the reaction coordinate with different transition temperatures. The ground state spectra of the RCs in active and inactive conformations report differences in the intraprotein electrostatic field, demonstrating that the dipole or charge distribution has changed. In addition, the electrochromic shift associated with the Q(A)(-) to Q(B) electron transfer at low temperature was characterized. The electron-transfer rate from Q(B)(-) to P(+) was measured at cryogenic temperature and is similar to the rate at room temperature, as expected for an exothermic, electron tunneling reaction in RCs.

Adaptation, Physiological↗
PubMed2001

Structural revision of isovalertatins M03, M13, and M23 isolated from the culture of Streptomyces luteogriseus.

Three aminooligosaccharides, isovalertatins M03 (1), M13 (2), and M23 (3) were isolated and purified from the culture filtrate of Streptomyces luteogriseus. Their physicochemical properties, liquid chromatographic behavior, and spectroscopic data were in full accordance with the reported compounds [Xu, Q.; Wang, Q.; Lu, D. CN Patent 1100756, 1995; Chem. Abstr. 1995, 123, 110278n], but their structures were reinvestigated and revised by spectroscopic methods, including ESI multistage mass spectrometry and 2-dimensional NMR techniques.

Amines↗
PubMed2001

Characterization of single-stranded DNA on chitosan-modified electrode and its application to the sequence-specific DNA detection.

Single-strand DNA could bind with chitosan on a platinum electrode via forming a tight DNA-chitosan complex. The salt concentration of the ssDNA solution had an obvious effect on the surface coverage, the immobilization was remarkably reduced at high salt concentration. The sample ssDNA immobilized on the chitosan-modified electrode can hybridize efficiently with the complementary sequences and be successfully used for the sequence-specific DNA detection. The same results could be obtained using a gold or graphite electrode modified with chitosan. The stability of this electrode has been also discussed.

Biopolymers↗
PubMed2001

Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study.

BACKGROUND: Chronic infections have been implicated in the pathogenesis of atherosclerosis, yet from an epidemiological perspective, this concept remains controversial. METHODS AND RESULTS: The Bruneck Study is a prospective population-based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to 79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were thoroughly assessed by high-resolution duplex scanning. The presence of chronic respiratory, urinary tract, dental, and other infections was ascertained by standard diagnostic criteria. Chronic infections amplified the risk of atherosclerosis development in the carotid arteries. The association was most pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex-adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to 6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It remained independently significant after adjustment for classic vascular risk attributes and extended to low-risk individuals free of conventional risk factors. Among subjects with chronic infections, atherosclerosis risk was highest in those with a prominent inflammatory response. Markers of systemic inflammation, such as soluble adhesion molecules and circulating bacterial endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to mycobacterial heat-shock protein 65 were elevated in subjects with chronic infections and predictive of an increased risk of atherosclerosis. CONCLUSIONS: The present study provides solid evidence for a role of common chronic infections in human atherogenesis. Induction of systemic inflammation and autoimmunity may be potential pathophysiological links.

Adult↗
PubMed2001

Stereocontrolled total synthesis of alkaloid G via the oxy-anion Cope rearrangement and improved total synthesis of (+)-ajmaline.

[figure: see text] The oxy-anion Cope rearrangement followed by protonation of the enolate which resulted under conditions of kinetic control has been employed to generate the key asymmetric centers at C(15), C(16), and C(20) in alkaloid G (1) and (+)-ajmaline (2) in a highly stereocontrolled fashion. The aldehyde 7b from this process has been converted into alkaloid G (1) and (+)-ajmaline (2) in 36% and 13% overall yields (11 reaction vessels from 3), respectively.

Ajmaline↗
PubMed2001

Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1.

OBJECTIVE: We studied the effects of temporary myocardial ischemia and reperfusion on myocyte injury and ventricular remodelling in wildtype and intercellular adhesion molecule-1- (ICAM-1) deficient mice. METHODS: ICAM-1-/- and ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subsequent reperfusion for 2 h, 1 week and 3 weeks, respectively. The evaluation of tissue damage and scar size was performed with histological sections stained with hematoxilin and eosin. Serum levels of troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were evaluated as an index of cardiac cellular damage. Immunohistological analysis was employed to determine cell compositions in ischemic regions. RESULTS: After myocardial ischemia (30 min) and 2 h reperfusion, elevation in serum troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were found in both groups, but significantly reduced in ICAM-1-/- mice compared with wildtype mice (P<0.05). Absence of a functional ICAM-1 gene in ICAM-1-/- mice resulted in a marked reduction of ischemia-reperfusion injury at the early stage. The damage score and size of the infarct area were lower in ICAM-1 -/- mice by 30 min of ischemia and 2 h of reperfusion (1.4+/-0.54 vs. 2.4+/-0.47, P<0.05). The percentage of MAC-1-positive cells in the ischemic region and the border zone was also significantly diminished in groups of ICAM-1-/- mice. Surprisingly, the scar size in ventricles in animals 1 or 3 weeks after ischemia was similar between ICAM-1-/- and ICAM-1+/+ mice, although the number of infiltrated MAC-1 positive cells in the scar in wildtype mice was higher. CONCLUSION: Our results demonstrate that the absence of ICAM-1 expression results in less myocardial damage induced by ischemia-reperfusion at the early stage, but does not influence the size of myocardial infarction and scar formation.

Animals↗
PubMed2001

Selective roles of retinoic acid receptor and retinoid x receptor in the suppression of apoptosis by all-trans-retinoic acid.

Retinoic acids exert profound effects on many biological processes including cell proliferation, differentiation, and morphogenesis. We previously reported that all-trans-retinoic acid (t-RA) protected mesangial cells from H(2)O(2)-triggered apoptosis by suppressing the activator protein 1 (AP-1) pathway. It was via inhibition of c-fos and c-jun expression and suppression of c-Jun N-terminal kinase (JNK) activation. In this report, we investigated the involvement of retinoic acid receptor (RAR) and retinoid X receptor (RXR) in the antiapoptotic effect of t-RA in H(2)O(2)-exposed cells. We found that pretreatment with RAR pan-antagonist (AGN193109) or RXR pan-antagonist (HX531) attenuated the antiapoptotic effect of t-RA. Similarly, transient transfection with a dominant-negative mutant of RAR or a dominant-negative RXR diminished the antiapoptotic effect of t-RA. Both RAR and RXR antagonists reversed the suppressive effect of t-RA on AP-1 activity. However, the roles of RAR and RXR in the suppression of AP-1 components by t-RA were found to be different. RAR antagonist reversed the suppressive effect of t-RA on both c-fos and c-jun, whereas RXR antagonist reversed the effect of t-RA on c-fos but not c-jun. Furthermore, suppression of JNK activation by t-RA was observed even in the presence of RAR and RXR antagonists. Consistently, suppression of JNK by t-RA was not affected by overexpression of either the dominant-negative RAR or the dominant-negative RXR. These data elucidated that the antiapoptotic effect of t-RA is mediated by both nuclear receptor-dependent and -independent mechanisms.

Animals↗
PubMed2001

Alkyne-based, highly stereo- and regioselective synthesis of stereodefined functionalized vinyl tellurides.

(Z)-beta-Aryltellurovinylphosphonates and (Z)-beta-aryltellurovinyl sulfones were synthesized via the highly stereoselective anti-hydrotelluration of 1-alkynylphosphonates and 1-alkynyl sulfones. The configurations of these compounds were characterized via 1H NMR spectra or NOESY experiments and by X-ray diffraction analysis; (E)-beta-aryltellurovinyl sulfones were obtained with the reaction of sodium aryltellurate with (E)-2-iodovinyl sulfones to confirm the stereochemistry of the above anti-hydrotelluration. When the tandem reaction of alkynes with diaryl ditellurides and sodium arylsulfinates was carried out in AcOH/H2O (4/1), the corresponding (E)-beta-aryltellurovinyl sulfones were obtained in one step in good yields. This reaction is highly regio- and stereoselective and proceeds by using arylsulfinate as the sulfonyl radical precursor and diaryl ditellurides as free radical acceptors. (E)-1-Iodo-2-aryltelluroalkenes can be obtained by the anti-addition of ArTeI with terminal alkynes in THF. The stereochemistry of compound 17b was also determined by X-ray diffraction analysis.

Journal Article↗
PubMed2001

Stability Characteristics of Dispersed Oil Droplets Prepared by the Microchannel Emulsification Method.

A novel emulsification method, microchannel (MC) emulsification, was developed for making monodispersed regular-sized droplets in our laboratory. An oil-in-water dispersed system, in which phosphate buffer was used as the continuous phase, sodium dodecyl sulfate (SDS) as the surfactant, and clove oil as the dispersed phase, was prepared by this technique. The average diameter of oil droplets was about 20 µm, with a narrow size distribution. The stability characteristics of the dispersed oil droplets were investigated by an optical microscope and kinetic light scattering method. The stability of the dispersed oil droplets depended on the SDS concentration. When the SDS concentration was above the critical micelle concentration (CMC), the turbidity of the dispersed solution sharply increased at the initial stage. Optical microscopic observation has confirmed that a part of the oil droplets broke up with time, and submicrometer droplets appeared. On the other hand, when the SDS concentration was below the CMC, the turbidity of the dispersed solution had little change in the initial stage, showing that the oil droplets were very stable. The effect of ion concentration was also examined. The results showed that the stability of the oil droplets depended on the balance of the Van der Waals attraction and electrical repulsion between the oil droplets in low ion concentration. Copyright 2001 Academic Press.

Journal Article↗
PubMed2001

Smooth muscle cell apoptosis in arteriosclerosis.

Arteriosclerosis, a paradigmatic age-related disease, encompasses (spontaneous) atherosclerosis, restenosis after percutaneous transluminal coronary angioplasty, autologous arterial or vein graft arteriosclerosis and transplant arteriosclerosis. In all types of arteriosclerosis, vascular smooth muscle cell (SMC) accumulation in the intima is a key event, but abundant evidence also indicates the importance of SMC apoptosis in the development of arteriosclerosis. Because SMC proliferation and apoptosis coincide in arteriosclerotic lesions, the balance between these two processes could be a determinant during vessel remodeling and disease development. Various stimuli, including oxidized lipoproteins, altered hemodynamic stress and free radicals, can induce SMC apoptosis in vitro. As risk factors for arteriosclerosis, these stimuli may also lead to vascular cell apoptosis in vivo. The presence of apoptotic cells in atherosclerotic and restenotic lesions could have potential clinical implications for atherogenesis and contributes to the instability of the lesion. Based on the progress in this field, this review focuses on the mechanism and impact of SMC apoptosis in the pathogenesis of arteriosclerosis and highlights the role of biomechanical stress in SMC apoptosis.

Animals↗
PubMed2001

Expression, regulation, and function of inhibitor of apoptosis family genes in rat mesangial cells.

BACKGROUND: The inhibitor of apoptosis (IAP) family of proteins regulates programmed cell death triggered by various stimuli. The purpose of this investigation was to examine the expression, regulation, and function of IAP genes in cultured rat mesangial cells. METHODS: Basal and inducible expression of c-IAP1, c-IAP2, XIAP, and TIAP mRNAs was examined in mesangial cells, isolated glomeruli, and other cell lines under unstimulated and tumor necrosis factor-alpha (TNF-alpha)-stimulated conditions. To examine a role of nuclear factor-kappa B (NF-kappa B) in the regulation of IAPs, expression of IAPs in NF-kappa B-inactive mesangial cells was compared with that in wild-type cells. To investigate roles of IAPs in mesangial cell apoptosis, NF-kappa B--inactive cells were stably supertransfected with c-IAP1 or c-IAP2, and the susceptibility of these cells to TNF-alpha--induced apoptosis was evaluated quantitatively. RESULTS: Substantial, constitutive expression of c-IAP2, XIAP, and TIAP was observed in serum-deprived rat mesangial cells and c-IAP2 and XIAP in isolated normal rat glomeruli. In response to TNF-alpha, expression of c-IAP1 and c-IAP2 was induced in HeLa cells and ECV304 endothelial cells, but not in mesangial cells. In contrast to previous reports on other cell types, the expression of IAPs in rat mesangial cells was independent of NF-kappa B; that is, expression levels of IAPs in NF-kappa B--inactive cells were same as those in NF-kappa B--active cells under both unstimulated and TNF-alpha--stimulated conditions. Even without the induction of IAPs, NF-kappa B--active mesangial cells were more resistant to TNF-alpha--induced apoptosis than NF-kappa B--inactive cells. Interestingly, overexpression of either c-IAP1 or c-IAP2 completely compensated for the lack of resistance to apoptosis in NF-kappa B--inactive cells. CONCLUSIONS: IAPs are constitutively expressed in cultured rat mesangial cells and isolated normal rat glomeruli. IAPs can contribute to the survival of rat mesangial cells, but unexpectedly, these molecules are not involved in the TNF-alpha--induced, NF-kappa B--dependent cytoprotection in this cell type.

Animals↗