Crystal structure of the Rhizomucor miehei aspartic proteinase.
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Aspartic Acid Endopeptidases↗
Biomedical subjects
Z Jia
Publications and source records attributed to Z Jia.
Triterpenoid saponins from Vaccaria segetalis.
Four novel triterpenoid saponins were isolated from the seeds of Vaccaria segetalis. Their structures were established as vaccaroside A, gypsogenic acid-28-O-beta-D- glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-[beta-D- glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; vaccaroside B, gypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->2)-[3-hydroxyl-3- methylglutaroyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-[beta-D- glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; vaccaroside C, 23-O-beta-D-glucopyranosyl-gypsogenic acid-28-O-beta-D- glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)- [beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside and vaccaroside D, 3,4-secogypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->3)- [beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside by a combination of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC and NOESY) studies and chemical degradation.
Carbohydrate Conformation↗
Triterpenoid saponins and sapogenins from Vaccaria segetalis.
Four new triterpenoid saponins, vaccarosides E, F, G and H were isolated from the seeds of Vaccaria segatalis and were respectively defined to be 3-O-beta-D-galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] 3beta,4chi,16chi-trihydroxy-23-norolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] gypsogenin 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl (1-->3)]-beta-D-4-O-acetylfucopyranoside; and 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] 3beta,4chi-dihydroxy-23norolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2) -chi-L-arabinofuranosyl-(1-->3)]-beta-D-4-O-acetyfucopyranoside. Their structures were established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC AND NOESY), FAB-MS and ESI-MS studies as well as chemical strategies and enzymatic degradation. The new aglycones of two of the saponins have been designated as segetalic acid and vaccaric acid, respectively.
Carbohydrate Conformation↗
Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP.
We have previously disrupted the ionotropic glutamate receptor type 2 gene (GluR2) using gene targeting in embryonic stem cells and generated mice which lacked the GluR2 gene product. Neurophysiological analyses of these mice showed a markedly enhanced long-term potentiation (LTP) and a 9-fold increase in kainate induced Ca2+ permeability in the hippocampus. Here, we analyze the behavioral and neuroanatomical consequences of GluR2 deficiency in homozygous null mutant and age-matched littermate control mice. We show that despite unaltered gross brain morphology, several aspects of behavior were abnormal in the mutants. Object exploration, rearing, grooming and locomotion were altered in the novel arena. Eye-closure reflex, motor performance on the rotating rod and spatial and non-spatial learning performance in the water maze were also abnormal in the mutants. These abnormalities together with the widespread expression pattern of GluR2 in most excitatory CNS pathways suggest that the absence of GluR2 leads to neurological phenotypes associated with not only the hippocampus but several other brain regions potentially including the cortex and cerebellum. We speculate that GluR2 mutant mice suffer from an overall non-specifically increased excitability that may alter cognitive functions ranging from stimulus processing to motivation and learning.
Animals↗
Major triterpenoid saponins from saponaria officinalis
Two major triterpenoid saponins, named saponariosides A and B, were isolated from the whole plants of Saponaria officinalis and were respectively defined to be 3-O-beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-be ta-D-glucuronopyranosyl quillaic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L-rhamnopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)-beta-D-4-O-ac etylquinovopyranosyl-(1-->4)]-beta-D-fucopyranoside (1); 3-O-beta-D-galactopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-be ta-D-glucuronopyranosyl quillaic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L-rhamnopyranosyl-(1-->2)-[beta-D-4-O-acetylquinovopyranosyl-(1-->4)] -beta-D-fucopyranoside (2). Their structures were established on the basis of extensive NMR (DEPT, DQF-COSY, HOHAHA, HETCOR, HMBC, and NOESY) and MS studies as well as chemical degradation.
Journal Article↗
Use-dependent AMPA receptor block in mice lacking GluR2 suggests postsynaptic site for LTP expression.
The mechanisms responsible for enhanced transmission during long-term potentiation (LTP) at CA1 hippocampal synapses remain elusive. Several popular models for LTP expression propose an increase in 'use' of existing synaptic elements, such as increased probability of transmitter release or increased opening of postsynaptic receptors. To test these models directly, we studied a GluR2 knockout mouse in which AMPA receptor transmission is rendered sensitive to a use-dependent block by polyamine compounds. This method can detect increases during manipulations affecting transmitter release or AMPA receptor channel open time and probability, but shows no such changes during LTP. Our results indicate that the recruitment of new AMPA receptors and/or an increase in the conductance of these receptors is responsible for the expression of CA1 LTP.
Action Potentials↗
Expression of apolipoprotein(a) kringle IV type 9 in Escherichia coli: demonstration of a specific interaction between kringle IV type 9 and apolipoproteinB-100.
A number of studies have provided evidence that lipoprotein(a) [Lp(a)] assembly is a two-step process in which initial non-covalent interactions between apolipoprotein(a) [apo(a)] and apolipoproteinB-100 (apoB-100) precede specific disulfide bond formation. We have designed a construct encoding apo(a) kringle IV type 9 (KIV9) in which the unpaired cysteine at position 67 in this kringle is replaced with a tyrosine. The single kringle was expressed in bacteria and purified to homogeneity from cell homogenates. The purified derivative (designated KIV9deltaCys) was assessed for its ability to bind to purified human LDL. This interaction was detected either by ELISA using immobilized LDL or by column chromatography in which LDL binding to KIV9deltaCys immobilized on Ni2+-Sepharose was determined. In both cases, the interaction of KIV9deltaCys and LDL was observed. Further, we demonstrated that the binding interaction was sensitive to the addition of amino acids including lysine, the lysine analogue epsilon-aminocaproic acid, arginine, phenylalanine and proline, with arginine and lysine having the greatest inhibitory effect. Binding of KIV9deltaCys to an immobilized apoB peptide spanning residues 3732-3745 of apoB was also demonstrated by ELISA. As was the case for LDL, this binding interaction was sensitive to the addition of arginine and lysine. Computer modeling of KIV9 demonstrated an excellent fit with residues 3732-3738 (PSCKLDF) of the apoB peptide. The modeling predicts the presence of overlapping lysine and phenylalanine-binding pockets in KIV9 which explains the inhibitory effects of lysine, arginine and phenylalanine which were observed in the binding assays. In summary, this study represents the first demonstration that KIV9 can interact directly with LDL through non-covalent interactions which may contribute to the first step of Lp(a) formation.
Amino Acid Sequence↗
[Effects of lotensin and nitrendipine on plasma fibrinogen and platelet aggregation in hypertensive patients].
Plasma fibrinogen and platelet aggregation were measured by turbidimetric immunoassay, turbidimetry in 47 hypertensive patients and 20 normotensive control subjects. Among the 47 hypertensives, 24 cases were received lotensin and 23 nitrendipine. The plasma fibrinogen was increased and platelet aggregation enhanced in hypertensive patients before treatment. Platelet aggregation decreased after 8 weeks of treatment with lotensin or nitrendipine respectively. Lotensin decreased plasma fibrinogen whereas nitrendipine did not. It was concluded that both lotensin and nitrendipine decreased platelet aggregation; lotensin decreased plasma fibrinogen but nitrendipine did not.
Angiotensin-Converting Enzyme Inhibitors↗
[Expression of inducible nitric oxide synthase in atherosclerotic rabbits].
Atherosclerotic lesions contain vascular smooth cells and thus may have an increased capacity for generation of nitric oxide (NO) by inducible NO synthase (iNOS). Rabbits (n = 8) were raised for eight weeks by the atherogenic diet, then the aortic rings were captured. Contractive responsiveness to norepinephrine, changes of CGMP, expression of iNOS of aortic rings were examined in vitro. There was a substantial decrease in contractile responsiveness to norepinephrine (NE) (P < 0.05), a decrease of CGMP (P < 0.01) and an increase of expression of iNOS (P < 0.05), after L-arginine or sodium nitroprusside treatment. The contractile responsiveness to NE was attenuated (P < 0.01). The CGMP was increased ((P < 0.01). After NG-nitric arginine (L-NNA) treatment, those reaction were reversed. It implied that L-arginine/NO pathway obstructure might likely be another mechanism of atherosclerosis and atherosclerotic arteries and had an increased capacity for generation of NO by iNOS.
Animals↗
[Hepatic metastasis from advanced gallbladder carcinoma: clinicopathological study].
OBJECTIVE: To clarify the characteristics of the related clinicopathological factors in cases of liver metastasis from carcinoma of the gallbladder (LmGbCa), and to provide some insights into the surgical management of LmGbca. METHOD: One hundred fifty-nine patients with subserosal (ss) cancer were studied. RESULT: 31 (19.4%) of the patients were found to have LmGbCa. Clinicopathologically, LmGbCa cases showed significant correlations with hinf(3) (P < 0.05), a depth of invasion of more than ss (P < 0.05), ly(3) (P < 0.05), v(3) (P < 0.01), and the location of the primary lesion on hep or circ (P < 0.01). CONCLUSION: Hepatectomy of S4 and S5 segments should be used when 2 risk factors of liver metastases were found operatively, and radiation therapy or chemotherapy should be combined with resection when 1 risk factor of liver metastasis and lymphatic invasion was found.
Female↗
[Synthesis and evaluation of restricted access stationary phases].
The restricted access stationary phase (RAS) are a new type of chromatographic packing material having a hydrophobic interior covered with a hydrophilic barrier. The RAS is used for direct injection in high-performance liquid chromatography for determination of drugs in biological fluids. These stationary phases include internal surface reverse phase, semipermeable surface, shielded hydrophobic phase and mixed functional phase (MFP). A kind of MFP packing material was synthesized from a porous silica gel-introduction of hydrophobic phenyl phase and introduction of hydrophilic diol phase. The MFP of RAS, on which proteins were eluted in the void volume, while the drugs were retained and separated, can be used for direct injection analysis of hydrophilic and hydrophobic drugs in serum and plasma. The recovery of the drugs in human serum was almost 100% with good reproducibility.
Blood Proteins↗
Repair effect of phenylpropanoid glycosides on thymine radical anion induced by pulse radiolysis.
Repair effects on thymine radical anion by six phenylpropanoid glycosides (PPGs), isolated from Pedicularis species, were studied using pulse radiolysis method. The thymine radical anion was produced by the reaction of hydrated electron with thymine. PPGs were added into the thymine solution saturated with N(2). Kinetic analysis showed that transient absorption spectrum of thymine radical anion formed at first, and then after several microseconds of pulse radiolysis changed to that of PPG radical anion. The evidence indicated that thymine radical anion was repaired through one-electron transfer between the radical anion and PPG. Electrophilic phenyl-substituted unsaturated carboxylic group containing in PPGs' structure was able to capture electron from thymine radical anion before it undergo reversible protonation. The reaction rate constants of electron transfer from thymine radical anion to PPGs were within 1.16-2.29 x 10(9) dm(3) mol(-1) s(-1).
Journal Article↗
Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP.
Class I metabotropic glutamate receptors (mGluRs) have been postulated to play a role in synaptic plasticity. To test the involvement of one member of this class, we have recently generated mutant mice that express no mGluR5 but normal levels of other glutamate receptors. The CNS revealed normal development of gross anatomical features. To examine synaptic functions we measured evoked field EPSPs in the hippocampal slice. Measures of presynaptic function, such as paired pulse facilitation in mutant CA1 neurons, were normal. The response of mutant CA1 neurons to low concentrations of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) was missing, which suggests that mGluR5 may be the primary high affinity ACPD receptor in these neurons. Long-term potentiation (LTP) in mGluR5 mutants was significantly reduced in the NMDA receptor (NMDAR)-dependent pathways such as the CA1 region and dentate gyrus of the hippocampus, whereas LTP remained intact in the mossy fiber synapses on the CA3 region, an NMDAR-independent pathway. Some of the difference in CA1 LTP could lie at the level of expression, because the reduction of LTP in the mutants was no longer observed 20 min after tetanus in the presence of 2-amino-5-phosphonopentanoate. We propose that mGluR5 plays a key regulatory role in NMDAR-dependent LTP. These mutant mice were also impaired in the acquisition and use of spatial information in both the Morris water maze and contextual information in the fear-conditioning test. This is consistent with the hypothesis that LTP in the CA1 region may underlie spatial learning and memory.
Animals↗
Tolerance of low pH in Schizosaccharomyces pombe requires a functioning pub1 ubiquitin ligase.
A strain of Schizosaccharomyces pombe carrying a disrupted Na+/H+ antiporter gene (sod2::sup3-5), in addition to the common auxotrophic mutations, ade6-216, ura4-D18 and leu1-32, is highly sensitive to media adjusted to pH 6.9. Reversion analysis of this strain yielded a group of revertants capable of growth at pH 6.9. Two of the revertants elongated and failed to form colonies at pH 3.5. Genetic characterization of one of the pH-sensitive elongated strains, J227, showed the presence of two independently segregating mutations. One, pub1 (protein ubiquitin ligase 1), has recently been reported as an E3 protein ubiquitin ligase involved in cdc25 turnover. The second has been named elp3-1 (elongated at low pH). Genetic dissection of the original strain revealed that poor growth at high pH was due to the presence of the auxotrophic markers, suggesting a possible inhibitory effect of high pH on the function of permeases responsible for uptake of the necessary nutrients. Suppression of the high pH sensitivity required the presence of both the pub1-1 and elp3-1 mutations. While the pub1-1 mutation reduced the capacity of cells to tolerate relatively moderate concentrations of LiCl (3 mM) in liquid culture, it was capable of partially suppressing the extreme Li+ sensitivity caused by the sod2 disruption. Under these conditions, the growth of pub1-1 sod2::ura4 double mutant cells was improved over that of either pub1-1 or sod2::ura4 cells. The elp3-1 mutation had no effect on the Li+ tolerance in either wild-type or sod2::ura4 backgrounds. pub1-1 cells are elongated and incapable of colony formation at pH 3.5. In contrast, elp3-1 cells are elongated at pH 3.5 and pH 5.5 (the normal pH of minimal medium) but can form colonies under both conditions. J227 cells are significantly longer than either single mutant at pH 3.5 and do not form colonies but are visually similar to elp3-1 cells at pH 5.5. Complementation cloning in the J227 background yielded a genomic clone of pub1, allowing us to define the intron-exon structure of the gene. Sequences with high homology to the predicted amino acid sequence of pub1 have been identified in Saccharomyces cerevisiae (RSP5/NPI1), human (hRPF1), mouse (mNedd4), and rat (rNedd4). Based on the nature of our mutant selection, the pH-sensitive phenotype of the strains selected, and the known involvement of RSP5/ NPI1 in membrane permease turnover in S. cerevisiae, we hypothesize a role for pub1, either directly or indirectly, in regulating membrane transport processes. This is further supported by the broad range of effects that the pub1-1 mutation exerts on overall performance of cells at high and low external pH, and in the presence of toxic levels of Li+.
Amino Acid Sequence↗
Antifungal sterol biosynthesis inhibitors.
During the course of the last decade, the development of SBIs, and particularly sterol biomethylation inhibitors, has been based on the rational design approach. Successful though this approach has been in elucidating sterol biomethylation enzymology, its limitations are becoming apparent from the findings that: (i) 24,25-double bond metabolism gives rise to cholesterol and ergosterol in a mechanistically similar manner, (ii) 25-azasterols are harmful to human physiology, and (iii) side-chain modified sterols designed to inhibit the SMT enzyme in S. cerevisiae may be ineffective or operate by another kinetic mechanism in a related organism, rendering it therapeutically nonuseful. Nevertheless, it may be possible to ultimately capitalize on the unique aspects of sterol biomethylation chemistry and enzymology to design taxa-specific inhibitors. With increased understanding of the structure and function of SMT enzymes in different fungi, it should be possible to prepare novel mechanism-based inactivators to control SMT activity uniquely and with high specific activity.
Amino Acid Sequence↗
Triterpenoid saponins from Mimusops elengi.
A novel minor triterpenoid saponin mimusin (3-O-[beta-D-glucopyranosyl- (1-->6)-beta-D-glucopyranosyl]-2 beta,3 beta,6 beta,23-tetrahydroxyolean- 12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside was isolated from the seeds of Mimusops elengi, in addition to two known triterpenoid saponins, Mi-saponin A and 16 alpha-hydroxy Mi-saponin A. The structure of the minor saponin was established by comparing its 13C NMR and LS-MS linked-scan, ESI-MS data with FAB-MS of the mimusopsin isolated earlier from the same source.
Carbohydrate Conformation↗
[The usage of allograft nasal septal cartilage in partial laryngectomy].
Based on the experiment of five dogs, 22 cases of laryngeal carcinoma using allograft nasal septal cartilage as a framework for laryngeal defect after partial larygectomy are reported. After 5 years follow-up, the functions of phonation and respiration of 17 cases were satisfying and their phonatic loudness was raised remarkably. The method was used mainly for patients with T1 glottic carcinoma involving anterion commissure and selective T2, T3 glottic carcinoma. The advantages of allograft nasal septal cartilage in partial laryngectomy are discussed in comparison with auto nasal mucoseptal graft.
Aged↗
[Prevention and treatment of stroke after hypertension for ten years in Hunan Province].
In this single blind, randomized multiple center clinical trial, the patients care period was divided into two stages. In the first stage (1985, 1-1989, 12), 984 cases were observed for 5 years whereas in the second stage (1990, 1-1994, 12), 2080 cases were observed and were subdivided into two groups, treat group and control, both were followed up for 5 years. The results showed that the prevalence of hypertension increased gradually. In the second stage, the average of blood pressure of the treatment group, using nitrendipine, was lower than that of the control group. There was significant difference between the two groups (P < 0.05). In the treatment group, the stroke and death rates were also decreased significantly as compared with the control group and the first stage group (P < 0.01).
Antihypertensive Agents↗