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Biomedical subjects

Z Jia

Publications and source records attributed to Z Jia.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Chemical constituents of Pedicularis muscicola Maxim].

From an ethanolic extract of whole plants of Pedicularis muscicola four glycosidic compounds were isolated. On the basis of chemical and spectal methods, their structurdes were determined to be one lignan glycosied and three iridoid glycosides: syringaresinol-4"-O-beta-D-glucoside (1), sesamoside (2), phloyoside II (3) and caryoptoside (4). All the four compounds were isolated from P. muscicola for the first time, and the compounds 2 and 3 were obtained for the first time from Pedicularis genus.

Drugs, Chinese Herbal↗
PubMed1997

[Properties and applications of restricted access stationary phases].

Several types of restricted access stationary phases used for the analysis of drugs in biological fluids by direct injection into high-performance liquid chromatographic column are introduced in this paper with 20 references These new packings included internal surface reversed phase, semipermeable surface, shielded hydrophobic phase and mixed functional phase. The structural characteristics and the chromatographic properties of these packings are reviewed, especially with regard to their use in the assaying of drugs.

Chromatography, High Pressure Liquid↗
PubMed1997

Protein phosphatases: structures and implications.

Protein phosphatases are signal transducing enzymes that dephosphorylate intracellular proteins phosphorylated on serine, threonine, and tyrosine residues. This brief review surveys recently determined structures of members of the protein tyrosine phosphatase and protein serine/threonine phosphatase families. In each family, characteristic and distinct structures confer different enzymatic mechanisms in catalyzing dephosphorylation reactions. Within each family, however, there exists remarkable similarity in active-site conformation and catalytic mechanism despite, in some cases, little or no sequence homology. The crystal structures also provide the basis for understanding the substrate binding specificity, inhibition by physiologically relevant compounds, and regulation of the protein phosphatases.

Animals↗
PubMed1997

[Effects of smoking on oxygen free radicals and fibrinolytic system].

UNLABELLED: The effects of smoking on SOD, MDA, t-PA, PAI-1 were studied in 20 healthy men (10 smokers and 10 nonsmokers). RESULTS: SOD decreased and MDA increased significantly in smokers. After acute smoking, SOD decreased and MDA increased significantly in all the subjects, t-PA and PAI-1 activities were increased immediately after acute smoking. There was a significant positive relationship between increased t-PA and SOD, whereas a significant negative relationship exists between increased t-PA and MDA. CONCLUSION: Smoking increases oxygen free radicals. The release of t-PA is decreased in smokers, that might be resulted from the increases of oxygen free radicals.

Adult↗
PubMed1996

Small molecule interactions with protein-tyrosine phosphatase PTP1B and their use in inhibitor design.

We have previously shown that a small peptide bearing the hydrolytically stable phosphotyrosyl (pTyr) mimetic, (difluorophosphonomethyl) phenylalanine (F2Pmp), is an extremely potent inhibitor of PTP1B, with an IC50 value of 100 nM [Burke, T. R., Kole, H. K., & Roller, P. P. (1994) Biochem. Biophys. Res. Commun. 204, 129-134]. We further demonstrated that removal of the peptide portion and incorporation of the difluorophosphonomethyl moiety onto a naphthalene ring system, but not a phenyl ring system, resulted in good inhibitory potency [Kole, H. K., Smyth, M. S., Russ, P. L., & Burke, T. R., Jr. (1995) Biochem, J. 311, 1025-1031]. In order to understand the structural basis for this inhibition, and to aid in the design of further analogs, we solved the X-ray structure of [1, 1-difluoro-1-(2-naphthalenyl)-methyl]phosphonic acid (6) complexed within the catalytic site of PTP1B, solved to 2.3 A resolution. In addition to showing the manner in which the phosphonate group is held within the catalytic site, the X-ray structure also revealed extensive hydrophobic interactions with the naphthalene ring system, beyond that possible with an analog bearing a single phenyl ring. It is further evident that, of the two fluorine atoms, the pro-R alpha-fluorine interacts with the enzyme to a significantly greater degree than the pro-S alpha-fluorine, forming a hydrogen bond to Phe 182. On the basis of a computer-assisted molecular modeling analysis, it was determined that addition of a hydroxyl to the naphthyl 4-position, giving [1, 1-difluoro-1-[2-(4-hydroxynaphthalenyl)] methyl]phosphonic acid (8), could potentially replace a water molecule situated in the PTP1B-6 complex, thereby allowing new hydrogen-bonding interactions with Lys 120 and Tyr 46. Compound 8 was therefore prepared and found to exhibit a doubling of affinity (Ki = 94 microM) relative to parent unsubstituted 6 (Ki = 179 microM), supporting, in principle, the development of high-affinity ligands based on molecular modeling analysis of the enzyme-bound parent.

Binding Sites↗
PubMed1996

Structural basis for the binding of a globular antifreeze protein to ice.

Antifreeze proteins (AFPs) have the unique ability to adsorb to ice and inhibit its growth. Many organisms ranging from fish to bacteria use AFPs to retard freezing or lessen the damage incurred upon freezing and thawing. The ice-binding mechanism of the long linear alpha-helical type I AFPs has been attributed to their regularly spaced polar residues matching the ice lattice along a pyramidal plane. In contrast, it is not known how globular antifreeze proteins such as type III AFP that lack repeating ice-binding residues bind to ice. Here we report the 1.25 A crystal structure of recombinant type III AFP (QAE isoform) from eel pout (Macrozoarces americanus), which reveals a remarkably flat amphipathic ice-binding site where five hydrogen-bonding atoms match two ranks of oxygens on the [1010] ice prism plane in the <0001> direction, giving high ice-binding affinity and specificity. This binding site, substantiated by the structures and properties of several ice-binding site mutants, suggests that the AFP occupies a niche in the ice surface in which it covers the basal plane while binding to the prism face.

Animals↗
PubMed1996

Functional expression of the Schizosaccharomyces pombe Na+/H+ antiporter gene, sod2, in Saccharomyces cerevisiae.

In the fission yeast, Schizosaccharomyces pombe, tolerance to high sodium and lithium concentrations requires the functioning of the sod2, Na+/H+ antiporter. We have directly measured the activity of this antiporter and demonstrated reconstitution of the activity in gene deletion strains. In addition, we have shown that it can be transferred to, and its antiporter activity detected in, the budding yeast, Saccharomyces cerevisiae, where it also confers sodium and lithium tolerance. Proton flux through the S. pombe Na+/H+ antiporter was directly measured using microphysiometry. The direction of transmembrane proton flux mediated by this antiporter was reversible, with protons being imported or exported in response to the external concentration of sodium. This bidirectional activity was also detected in S. cerevisiae strains expressing sod2 and expression of this gene complemented the sodium and lithium sensitivity resulting from inactivation of the ENA1/PMR2 encoded Na+-exporting ATPases. This suggests that antiporters or sodium pumps can be utilized interchangeably by S. cerevisiae to regulate internal sodium concentration. Potent inhibitors of mammalian Na+/H+ exchangers were found to have no effect on sod2 activity. The proton flux mediated by sod2 was also found to be unaffected by perturbation of membrane potential or the plasma membrane proton gradient.

Amiloride↗
PubMed1996

Scavenging effects of phenylpropanoid glycosides from Pedicularis on superoxide anion and hydroxyl radical by the spin trapping method(95)02255-4.

The scavenging activities of six phenylpropanoid glycosides, i.e. leucosceptoside A and martynoside, isolated from Pedicularis alashanica Maxim, verbascoside, and pediculariosides A, M and N isolated from Pedicularis striata Pall ssp. arachnoidea Franch Tsoong, on superoxide anion and hydroxyl radicals have been studied by the spin trapping method. The results demonstrated that the number of phenolic hydroxyl groups in the structures of the phenylpropanoid glycosides is related to their scavenging activities. The scavenging effects of the phenylpropanoid glycosides possessing two o-dihydroxyl groups were stronger than the effects of the compounds possessing two o-hydroxy-methoxy groups.

Cyclic N-Oxides↗
PubMed1996

Mechanism and structural requirements for transformation of substrates by the (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase from Saccharomyces cerevisiae.

The mechanism of action and active site of the enzyme (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase (SMT) from Saccharomyces cerevisiae strain GL7 have been probed with AdoMet, (S)-adenosyl-L-homocysteine, a series of 35 sterol substrates as acceptor molecules and a series of 10 substrate and high energy intermediate (HEI) sterol analogues as inhibitors of biomethylation. The SMT was found to be selective for sterol, both regio- and stereochemically. The presence of an unhindered 24,25-bond, an equatorially-oriented polar group at C-3 (which must act as a proton acceptor) attached to a planar nucleus and a freely rotating side chain were obligatory structural features for sterol binding/catalysis; no essential requirement or significant harmful effects could be found for the introduction of an 8(9)-bond, 14 alpha-methyl or 9 beta,19-cyclopropyl group. Alternatively, methyl groups at C-4 prevented productive sterol binding to the SMT. Initial velocity, product inhibition, and dead-end experiments demonstrated a rapid-equilibrium random bi bi mechanism. Deuterium isotope effects developed from SMT assays containing mixtures of [3-3H]zymosterol with AdoMet or [methyl-2H3]AdoMet confirmed the operation of a random mechanism, kappa H/kappa D = 1.3. From this combination of results, the spatial relationship of the sterol substrate to AdoMet could be approximated and the topology of the sterol binding to the SMT thereby formulated.

Cell Fractionation↗
PubMed1996

Enhanced LTP in mice deficient in the AMPA receptor GluR2.

AMPA receptors (AMPARs) are not thought to be involved in the induction of long-term potentiation (LTP), but may be involved in its expression via second messenger pathways. However, one subunit of the AMPARs, GluR2, is also known to control Ca2+ influx. To test whether GluR2 plays any role in the induction of LTP, we generated mice that lacked this subunit. In GluR2 mutants, LTP in the CA1 region of hippocampal slices was markedly enhanced (2-fold) and nonsaturating, whereas neuronal excitability and paired-pulse facilitation were normal. The 9-fold increase in Ca2+ permeability, in response to kainate application, suggests one possible mechanism for enhanced LTP. Mutant mice exhibited increased mortality, and those surviving showed reduced exploration and impaired motor coordination. These results suggest an important role for GluR2 in regulating synaptic plasticity and behavior.

Animals↗
PubMed1996

Repair of dGMP hydroxyl radical adducts by verbascoside via electron transfer: a pulse radiolysis study.

The repair activity of verbascoside (VER), isolated from Pedicularis spicata, towards the oxidizing hydroxyl radical adduct of dGMP and its reaction mechanism were studied using pulse radiolysis. Upon pulse radiolysis of nitrous oxide saturated aqueous solution of 2'-deoxyguanosine-5'-monophosphate (dGMP) and VER, it was found that the transient absorption spectrum of the hydroxyl adduct of dGMP decays with the formation of that of the phenoxyl radical of VER, several tens of microseconds after the electron pulse. From the formation kinetics of the phenoxyl radical of VER, the rate constant of the repair reaction was determined to be 1.12 x 10(9) dm(3) mol(-1) s(-1).

Antioxidants↗
PubMed1996

[Dashengbian (thesis on longevity) and its author].

Dashengbian was a very popular obstetric book in the 18th century. It once had a significant influence in history not only because it fairly well sumed up predecessors' experiences and filled in the gaps in the field of obstetrics, but also because it had an easy-reading, concise and practical contents. As for the author of the book, although many blockprinted editions were signed by Lay Buddhist Ji Zhai, his real name was unknown. This article holds that the book had been circulated for some time before it came out in the 54th year of Kang Xi reign which is in line with the manuscripts of Qian Long reign of the Qing dynasty and the names carried in its case records. According to other relevant data, the article believes that Lay Buddhist Ji Zhai was most likely to be Zhang Zhao, a scholar of the early Qing dynasty.

China↗
PubMed1996

Reaction of hydroxyl radical with phenylpropanoid glycosides from Pedicularis species: a pulse radiolysis study.

Using pulse radiolysis technique, the reaction between hydroxyl radical and 7 phenylpropanoid glycosides: echinacoside, verbascoside, leucosceptoside A, martynoside, pediculariosides A, M and N which were isolated from Pedicularis were examined. The rate constants of these reactions were determined by transient absorption spectra. All 7 phenylpropanoid glycosides react with hydroxyl radical at high rate constants within (0.97-1.91) x 10(10)L.mol-1.s-1, suggesting that they are effective hydroxyl radical scavengers. The results demonstrate that the numbers of phenolic hydroxyl groups of phenylpropanoid glycosides are directly related to their scavenging activities. The scavenging activities are likely related to o-dihydroxy group of phenylpropanoid glycosides as well.

Drugs, Chinese Herbal↗
PubMed1996

[Experimental study of the protective effects of astragalus and salvia miltiorrhiza bunge on glycerol induced acute renal failure in rabbits].

The astragalus and salvia miltiorrhiza bunge alcohol extracts were used in preventive treatment of glycerol induced acute renal failure (ARF) in rabbits. The experimental rabbits were divided: astragalus group (AB), salvia miltiorrhia bunge group (SM), two extracts mixture group (ABSM), and normol saline control group (C). The extracts, mixtures and normol saline were administrated before and after the induced ARF. The counts of Na, K, creatinine in urine and blood and urinary AAP, NAG were determinated during 24-14 days periodically in all 4 groups, and the renal tissues were taken from same periods for pathomorphological studies by microscopy and transmission electromicroscopy. The damage of the glycerol induced ARF was not only in the convolute tubules but also in the glomerulus. The glomerulor filtration rate reduced abruptly, and oligouria or auria developed. The study of renal functions and renal morphogy showed that the AB and ABSM groups were damaged more lesser and promptely repaired than the SM and C groups in the early stage. No glomerular sclerosis was noted in the AB, ABSM groups in later stage, but it occurred sporadically or diffusely in the SM, C groups. Therefore, astragalus is an ideal protective drug of traditional chinese medicine for ARF.

Acute Kidney Injury↗
PubMed1995

Framework residues 71 and 93 of the chimeric B72.3 antibody are major determinants of the conformation of heavy-chain hypervariable loops.

Structural analysis derived from the crystallographic study of the chimeric B72.3 antibody illustrated that some heavy-chain framework residues having atomic interactions with heavy-chain CDR residues may directly affect the conformation of CDR loops. For example, an alanine residue at H71 provides room for packing CDR2/CDR1 and lysine residues at H73 and H93 contribute a salt-bridge to aspartic acid at H55 in CDR2 and a hydrogen bond to the carbonyl group at H96 in CDR3, respectively. We have analysed the contribution of these framework residues to the TAG72-binding affinity. We altered these framework residues by site-directed mutagenesis, and determined the affinity of these mutant chimeric antibodies for the TAG72 antigen by solid phase radioimmunoassay. We found that a single amino acid substitution of alanine by phenylalanine at H71 or lysine by isoleucine at H93, significantly reduced the binding affinity for the TAG72 antigen by 12 and 20-fold, respectively, whereas the substitution of lysine by alanine at H73 reduced the binding affinity only two-fold. Our results indicate that heavy-chain framework residues alanine at H71 and lysine at H93 of the chimeric B72.3 antibody are the major determinants of the conformation of heavy-chain CDR2/CDR1 and CDR3 loops, whereas the salt-bridge between lysine at H73 and aspartic acid at H55 is less important. The hydrogen bond between two framework residues, glutamine at H5 and serine at H25 does not affect any CDR conformation. Our results will thus be of importance especially when the humanized B72.3 antibody is constructed by grafting the CDR loops to a human framework. The important framework region interactions must be maintained in the final humanized antibody.

Amino Acid Sequence↗
PubMed1995

Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.

The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the period and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.

Binding Sites↗
PubMed1995

Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.

The lysosomal cysteine proteinase cathepsin B (EC 3.4.22.1) plays an important role in protein catabolism and has also been implicated in various disease states. The crystal structures of two forms of native recombinant rat cathepsin B have been determined. The overall folding of rat cathepsin B was shown to be very similar to that of the human liver enzyme. The structure of the native enzyme containing an underivatized active site cysteine (Cys29) showed the active enzyme conformation to be similar to that determined previously for the oxidized form. In a second structure Cys29 was derivatized with the reversible blocking reagent pyridyl disulfide. In this structure large side chain conformational changes were observed for the two key catalytic residues Cys29 and His199, demonstrating the potential flexibility of these side chains. In addition the structure of the complex between rat cathepsin B and the inhibitor benzyloxycarbonyl-Arg-Ser(O-Bzl) chloromethylketone was determined. The complex structure showed that very little conformational change occurs in the enzyme upon inhibitor binding. It also allowed visualization of the interaction between the enzyme and inhibitor. In particular the interaction between Glu245 and the P2 Arg residue was clearly demonstrated, and it was found that the benzyl group of the P1 substrate residue occupies a large hydrophobic pocket thought to represent the S'1 subsite. This may have important implications for structure-based design of cathepsin B inhibitors.

Amino Acid Chloromethyl Ketones↗