Biomedical subjects

Yu Huang

Publications and source records attributed to Yu Huang.

At least 73 records · Page 4Linked to original sources

PubMed2004

Adeno-associated viral vector delivers cardiac-specific and hypoxia-inducible VEGF expression in ischemic mouse hearts.

It has been shown that the adeno-associated virus (AAV) vector can deliver the VEGF gene efficiently into the ischemic mouse myocardium. However, the AAV genomes can be found in extracardiac organs after intramyocardial injection. To limit unwanted VEGF expression in organs other than the heart, we tested the use of the cardiac myosin light chain 2v (MLC-2v) promoter and the hypoxia-response element to mediate cardiac-specific and hypoxia-inducible VEGF expression. An AAV vector, MLCVEGF, with 250 bp of the MLC-2v promoter and nine copies of the hypoxia-response element driving VEGF expression, was constructed. Gene expression was studied in vitro by infection of rat cardiomyocytes, rat skeletal myocytes, and mouse fibroblasts with the vector and in vivo by direct injection of the vector into normal and ischemic mouse hearts. With MLCVEGF infection, VEGF expression was higher in cardiomyocytes than the other two cell lines and was hypoxiainducible. VEGF expression was also higher in ischemic hearts than in normal hearts. No VEGF expression was detectable in organs with detectable MLCVEGF vectors other than the heart. MLCVEGF-injected ischemic hearts had more capillaries and small vessels around the injection site, smaller infarct size, and better cardiac function than the negative controls. Hence, MLCVEGF can mediate cardiac-specific and hypoxia-inducible VEGF expression, neoangiogenesis, infarct-size reduction, and cardiac functional improvement.

Animals↗

PubMed2004

Expression of TRPC homologs in endothelial cells and smooth muscle layers of human arteries.

TRPC channels are a group of Ca(2+)-permeable nonselective cation channels that mediate store-operated and/or agonist-stimulated Ca(2+) influx in a variety of cell types. In this study, we extensively examined the expression patterns of TRPC homologs in human vascular tissues. RT-PCR amplified cDNA fragments of TRPC1 (505 bp), TRPC3 (372 bp), TRPC4 (499 bp), TRPC5 (325 bp), TRPC6 (509 bp), and TRPC7 (187 bp) from RNA isolated from cultured human coronary artery endothelial cells. In situ hybridization yielded strong labeling of TRPC1,3-6 in the endothelial and smooth muscle cells of human coronary and cerebral arteries. TRPC7 labeling was exclusively found in endothelial cells but not in smooth muscle cells. Results from immunohistochemical staining were consistent with those from in situ hybridization. Similar expression patterns of TRPC homologs were also observed in arterioles and vaso vasora. In conclusion, our study indicates that TRPC homologs are widely expressed in human vessels of all calibers, including medium-sized coronary arteries and cerebral arteries, smaller-sized resistance arteries, and vaso vasora. These results suggest a ubiquitous role of TRPC homologs in regulating blood supply to different regions and in controlling arterial blood pressure.

Adolescent↗

PubMed2004

Mnb/Dyrk1A phosphorylation regulates the interaction of dynamin 1 with SH3 domain-containing proteins.

Mnb/Dyrk1A is a proline-directed serine/threonine kinase implicated in Down's syndrome. Mnb/Dyrk1A was shown to phosphorylate dynamin 1 and alter its interactions with several SH3 domain-containing endocytic accessory proteins. To determine the mechanism of regulation, we mapped the Mnb/Dyrk1A phosphorylation sites in dynamin 1. Using a combination of deletion mutants and synthetic peptides, three potential Mnb/Dyrk1A phosphorylation sites (S778, S795, and S857) were first identified. Phosphorylation at S795 and S857 was confirmed in full-length dynamin 1, and S857 was subsequently determined to be the major Mnb/Dyrk1A phosphorylation site in vitro. Phosphorylation at S857 was demonstrated to be the basis for altering the binding of dynamin 1 to amphiphysin 1 and Grb 2 by site-directed mutants mimicking phosphorylation. Furthermore, S857 of dynamin 1 is phosphorylated by the endogenous kinase in brain extracts and in PC12 cells. In PC12 cells, the state of S857 phosphorylation is dependent on membrane potentials. These results suggest that S857 phosphorylation is a physiological event, which regulates the binding of dynamin 1 to SH3 domain-containing proteins. Since S857 is unique to dynamin 1xa isoforms, Mnb/Dyrk1A regulation of dynamin 1 is expected to be specific to these spliced variants.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries.

Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K+-containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K+ channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K+-containing solutions (60 mmol/L), suggesting that K+ channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K+ (K(v)) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K+ channels with glibenclamide (3 micromol/L), apamin (1 micromol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 micromol/L), or Ba2+ (3 micromol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K(v) channel activation in vascular smooth muscle cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2004

Attenuated endothelium-mediated relaxation by acteoside in rat aorta: Role of endothelial [Ca2+]i and nitric oxide/cyclic GMP pathway.

Acteoside and other phenylethanoid glycoside are contained in many plants that are widely used in traditional Chinese herbal medicine. Acteoside possesses multiple biological actions. Its effect on the vascular system is, however, incompletely understood. This study was aimed to investigate the role of endothelial [Ca2+]i, nitric oxide (NO), and cyclic GMP in acteoside-induced inhibition of endothelial NO-mediated relaxation in rat aorta. Acteoside reduced endothelial NO-dependent relaxation induced by acetylcholine (Ach) or A23187. Acteoside inhibited Ach-stimulated increase in tissue content of cyclic GMP in endothelium-intact rings. L-NNA abolished the stimulatory effect of Ach. Treatment with acteoside significantly suppressed bradykinin-induced increase in [Ca2+]i of cultured rat aortic endothelial cells. Acute exposure to acteoside (30 microM) did not affect the expression of eNOS mRNA in endothelium-intact rings. In summary, acteoside impairs endothelial NO-mediated aortic relaxation partially through inhibition of agonist-induced endothelial Ca2+ mobilization and Ca2+-dependent NO production and subsequent suppression of cyclic GMP formation. This novel pharmacological action if occurring in small vessels in vivo, may contribute to the reported anti-inflammatory effect of acteoside against NO-mediated vascular permeability-related acute edema.

Animals↗

PubMed2004

Cellular mechanism for potentiation of Ca2+-mediated Cl- secretion by the flavonoid baicalein in intestinal epithelia.

Flavonoids belong to a large group of plant polyphenols that are consumed daily in large amounts. Our previous findings have shown that baicalein, a major flavonoid derived from the medicinal herb Scutellariae radix, induces Cl(-) secretion across rat colonic mucosa. The current study examines the effect of baicalein on Cl(-) secretion in human colonic epithelial (T84) cells and its interaction with Ca(2+)- and cAMP-dependent secretagogues. We have employed a technique that allows concurrent monitoring of short-circuit current (I(SC)) and [Ca(2+)](i) in polarized epithelium. Basolateral application of baicalein induced a concentration-dependent increase in I(SC). The increase in I(SC) was because of Cl(-) secretion and was not accompanied by any discernible increase in [Ca(2+)](i). Baicalein acted synergistically with Ca(2+)- but not cAMP-dependent secretagogues. In the presence of baicalein, the carbachol and histamine induced increases in I(SC) that were markedly potentiated while increases in [Ca(2+)](i) were not significantly enhanced. Baicalein treatment uncoupled Cl(-) secretion from inhibitory effects normally generated by muscarinic activation. Baicalein treatment also resulted in increased cAMP content and activated PKA activity. Nystatin permeabilization studies revealed that baicalein stimulated an apical Cl(-) current but did not activate any basolateral K(+) current. These data suggest that baicalein potentiates Ca(2+)-mediated Cl(-) secretion through a signaling pathway involving cAMP and protein kinase A, most likely through the cystic fibrosis transmembrane conductance regulator in the apical membrane.

Antioxidants↗

PubMed2004

Estrogen and tamoxifen modulate cerebrovascular tone in ovariectomized female rats.

Postmenopausal estrogen deficiency increases the incidence of cerebrovascular disease. However, hormone replacement therapy is associated with an increased cardiovascular risk. Tamoxifen is a selective estrogen receptor modulator with estrogenic effects on cardiovascular risk factors, but its long-term impacts on cerebral vasculature are unknown. We hypothesized that chronic 17beta-estradiol or tamoxifen treatment exerted similar effects in reducing cerebrovascular tension in ovariectomized rats. We therefore determine whether (1) chronic 17beta-estradiol treatment could influence vasomotor activities, (2) chronic tamoxifen therapy could exert an estrogen-like or estrogen-antagonistic effect, and (3) acute exposure to estrogen could mimic the effect of 17beta-estradiol. Isometric tension was measured in cerebral arteries from female rat groups: control, ovariectomy, ovariectomy plus 17beta-estradiol treatment, ovariectomy plus tamoxifen treatment, and ovariectomized rats treated with tamoxifen and 17beta-estradiol. Ovariectomy enhanced cerebrovascular contractions to endothelin-1 or CaCl2, but not to U46619 or phenylephrine. 17beta-Estradiol therapy reversed these effects. Chronic tamoxifen treatment exerted estrogen-like actions by reversing ovariectomy-induced enhancement of vessel tone without antagonizing the effect of chronic 17beta-estradiol treatment. Ovariectomy enhanced the relaxing potency of nicardipine, and 17beta-estradiol treatment prevented this effect. Acute exposure to 10(-9) mol/L 17beta-estradiol or 10(-8) mol/L tamoxifen did not modulate contractions in rings from nonoperated female rats. In conclusion, ovariectomy differentially enhances agonist-induced cerebrovascular tone, an effect that was reversed by estrogen therapy. Tamoxifen does not act as an estrogen antagonist; instead, it functions as an estrogen agonist during estrogen deficiency. Thus, tamoxifen may confer beneficial effects similar to estrogen in cerebrovascular vessels.

Animals↗

PubMed2004

Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels.

BACKGROUND AND PURPOSE: Because of their mixed estrogen-agonist and estrogen-antagonist properties, selective estrogen receptor modulators (SERMs) are considered promising substitutes for hormone replacement therapy. Raloxifene and other SERMs confer estrogen-like cardiovascular protective effects but lack the carcinogenic activity of exogenous estrogen. However, little is known about the cerebrovascular action of raloxifene. Therefore, we studied the effects of raloxifene on the mechanisms regulating rat cerebral artery tone. METHODS: Ring segments of the isolated rat posterior communicating cerebral arteries were mounted in a microvessel myograph for measurement of isometric tension. Whole-cell L-type voltage-sensitive Ca2+ currents were recorded using the perforated patch-clamp technique. Raloxifene (0.1 to 10 micromol/L) reduced the contractile responses to U46619, phenylephrine, and endothelin-1 in normal Krebs solution or to CaCl2 in Ca2+-free, high K+-containing solution. Raloxifene-induced relaxation was identical in endothelium-intact and endothelium-denuded rings. ICI 182780 had no effect on raloxifene-induced relaxation. Raloxifene reduced L-type Ca2+ currents with a pD2 of 5.98+/-0.06, close to that (6.44+/-0.09) for raloxifene-induced relaxation of 60 mmol/L K+-contracted rings. CONCLUSIONS: This study demonstrates that raloxifene acutely relaxes rat cerebral arteries largely via an endothelium-independent mechanism, involving inhibition of Ca2+ influx through L-type Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2004

Nickel inhibits urocortin-induced relaxation in the rat pulmonary artery.

Urocortin relaxes rat pulmonary arteries partly through a cyclic AMP-dependent but Ca(2+) channel-independent mechanism. However, other participating mechanisms are relatively unknown. The present study was designed to examine whether the forward mode of Na(+)-Ca(2+) exchangers play a role in the relaxant responses to urocortin in isolated rat small pulmonary arteries. Endothelium-denuded rings were mounted on small vessel myographs for measurement of changes in isometric tension. Urocortin inhibited 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619)-induced contraction in a concentration-dependent manner and this inhibition was reversed by astressin, a corticotropin-releasing factor receptor antagonist. Micromolar concentrations of nickel (Ni(2+)) chloride, a putative inhibitor of the Na(+)-Ca(2+) exchanger, reduced the relaxant responses to urocortin. Urocortin-induced relaxation was abolished in a Na(+)-free solution, a condition that eliminates influence of the forward mode of Na(+)-Ca(2+) exchanger. In contrast, the relaxant responses to atrial natriuretic peptide or forskolin were unaffected by Ni(2+) or with removal of extracellular Na(+). The present results provide indirect evidence suggesting that stimulation of Na(+)-Ca(2+) exchangers may contribute to urocortin-induced endothelium-independent pulmonary artery relaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2004

Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G.

Canonical transient receptor potential (TRPC) channels are Ca2+-permeable nonselective cation channels that are widely expressed in numerous cell types. Seven different members of TRPC channels have been isolated. The activity of these channels is regulated by the filling state of intracellular Ca2+ stores and/or diacylglycerol and/or Ca2+/calmodulin. However, no evidence is available as to whether TRPC channels are regulated by direct phosphorylation on the channels. In the present study, TRPC isoform 3 (TRPC3) gene was overexpressed in HEK293 cells that were stably transfected with protein kinase G (PKG). We found that the overexpressed TRPC3 mediated store-operated Ca2+ influx and that this type of Ca2+ influx was inhibited by cGMP. The inhibitory effect of cGMP was abolished by KT5823 or H8. Point mutations at two consensus PKG phosphorylation sites (T11A and S263Q) of TRPC3 channel markedly reduced the inhibitory effect of cGMP. In addition, TRPC3 proteins were purified from HEK293 cells that were transfected with either wild-type or mutant TRPC3 constructs, and in vitro PKG phosphorylation assay was carried out. It was found that wild-type TRPC3 could be directly phosphorylated by PKG in vitro and that the phosphorylation was abolished in the presence of KT5823. The phosphorylation signal was greatly reduced in mutant protein T11A or S263Q. Taken together, TRPC3 channels could be directly phosphorylated by PKG at position T11 and S263, and this phosphorylation abolished the store-operated Ca2+ influx mediated by TRPC3 channels in HEK293 cells.

Calcium↗

PubMed2004

Inhibition of nitric oxide/cyclic GMP-mediated relaxation by purified flavonoids, baicalin and baicalein, in rat aortic rings.

The dried roots of Scutellaria baicalensis Georgi (Huangqin) are widely used in traditional Chinese medicine. We purified two flavonoids, baicalin and baicalein from S. baicalensis Georgi and examined their effects on isolated rat aortic rings. Baicalin (3-50 microM) inhibited endothelium/nitric oxide (NO)-dependent relaxation induced by acetylcholine (Ach) or cyclopiazonic acid (CPA). Baicalein at 50 microM abolished Ach-induced relaxation and markedly reduced CPA-induced relaxation. Treatment with 1mM L-arginine partially but significantly reversed the effects of baicalin (50 microM) or baicalein (50 microM) on Ach-induced relaxation. In endothelium-denuded rings, treatment with baicalin, baicalein or methylene blue partially inhibited relaxations induced by the NO donors, sodium nitroprusside (SNP) and hydroxylamine. Both flavonoids markedly reduced the increase in cyclic GMP levels stimulated by Ach in endothelium-intact rings and by SNP in endothelium-denuded rings. In contrast, exposure of endothelium-denuded rings to baicalin or baicalein did not affect relaxations induced by pinacidil or NS 1619, putative K+ channel activators. Neither flavonoids affected agonist-induced increase in the endothelial [Ca2+]i. Our results indicate that baicalin and baicalein attenuated NO-mediated aortic relaxation and cyclic GMP increases, likely through inhibition of NO-dependent guanylate cyclase activity.

Animals↗

PubMed2004

Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta.

The beneficial effect of estrogen on the vascular system is partly associated with its ability to reduce vascular contractility. Estrogen acutely activates large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) and inhibits L-type voltage-gated Ca(2+) channel (VGCC) in vascular smooth muscle cells. However, a long-term influence of estrogen, estrogen deficiency, or selective estrogen receptor modulators on gene expression of these ion channels is unclear. This study was therefore aimed to determine the relative mRNA expression levels of alpha- and beta-subunits of BK(Ca), K(V)1.5 subtype of delayed rectifier K(+) channel (K(V)), and alpha(1C) subunit of L-type VGCC in endothelium-denuded aortas from female rats by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Rats were divided into four experimental groups: (i) sham-operated control, (ii) ovariectomized, (iii) ovariectomized with 17 beta-estradiol treatment and (iv) ovariectomized with tamoxifen treatment. The results showed that ovariectomy decreased the mRNA expression of K(V)1.5 while it increased the mRNA expression of alpha(1C) subunit of L-type VGCC. Ovariectomy-induced modulation of gene expression of these ion channels was completely prevented in ovariectomized rats receiving chronic treatment with estrogen or tamoxifen. In contrast, the expression levels of genes encoding both alpha- and beta-subunits of BK(Ca) remained the same in the four animal groups. The present study has provided the first line of evidence suggesting the long-term beneficial effects of estrogen and tamoxifen therapy on vascular ion channel expressions, which may be an important mechanism by which the favorable modulation of vessel tone by estrogen or selective estrogen receptor modulators is mediated.

Animals↗

PubMed2004

Extracellular ATP facilitates flow-induced vasodilatation in rat small mesenteric arteries.

ATP can be released from endothelial cells, and this release is increased by intraluminal flow in blood vessels. In the present study, the effect of extracellular ATP (1 microM) on flow-induced vasodilatation was investigated in isolated and pressurized rat small mesenteric arteries. In the absence of extracellular ATP, only 46% of arteries developed dilatation in response to flow, and this response was both transient and unstable. In marked contrast, with ATP present, all vessels developed a prolonged and stable dilatation in response to flow. Even in the vessels that failed to respond to flow in the absence of ATP, dilatation could be stimulated once ATP was present. The ability of ATP to facilitate flow-induced vasodilatation was mimicked by UTP (1 microM), a P2Y agonist, or 3'-O-(4-benzoyl)benzoyl ATP (BzATP; 10 microM), an agonist for P2X1, P2X7, and P2Y11 purinoceptors. The involvement of P2X7 purinoceptors was further supported by the inhibitory effect of KN-62 (1 microM), a P2X7 antagonist, on the action of BzATP. P2X1 and P2X3 purinoceptors were not involved because their receptor agonist alpha,beta-methylene ATP had no effect. The facilitating effect of ATP on flow dilatation was also attenuated by the combined application of reactive blue 2 (100 microM), a P2Y antagonist, and suramin (100 microM), a nonselective P2X and P2Y antagonist. Furthermore, flow-induced dilatation obtained in the presence of ATP was reproducible. In contrast, in the additional presence of the ectonucleotidase inhibitor ARL-67156 (10 microM), although the first dilatation was normal, the responses to the second and later exposures to flow were greatly attenuated. The nonhydrolyzable ATP analogs adenosine-5'-(3-thiotriphosphate)trilithium salt (1 microM) and adenosine 5'-(beta,gamma-imido) triphosphate tetralithium salt hydrate (10 microM) had similar effects to those of ARL-67156. These data suggest that ATP acts through both P2X and P2Y purinoceptors to facilitate flow-induced vasodilatation and that ectonucleotidases prevent this effect by degrading ATP on the endothelial cell surface.

Adenosine Triphosphate↗

PubMed2004

Comparison of antioxidant activity and bioavailability of tea epicatechins with their epimers.

Canned and bottled tea drinks contain not only green tea epicatechins (GTE), namely (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC), but also four GTE epimers, namely (-)-gallocatechin gallate (GCG), (-)-catechin gallate (CG), (-)-gallocatechin (GC) and (-)-catechin (C). In the present study we examined the antioxidant activity and bioavailability of these epimers compared with their corresponding precursors. The epimerisation reaction was induced by autoclaving GTE extract derived from longjing green tea at 120 degrees C for 20 min. Isolation and purification of each GTE and epimer were accomplished by various column chromatographic and semi-preparative HPLC techniques. The antioxidant activity of each epimer with its corresponding GTE precursor was conducted in the three in vitro systems, namely human LDL oxidation, ferric reducing-antioxidant power (FRAP), and anti-2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assays. The results of all three assays demonstrated that CG had similar antioxidant activity with its precursor ECG, while GC was less potent as an antioxidant than its precursor EGC. Regarding EGCG and GCG, the antioxidant potency was similar for both LDL oxidation and DPPH free radical assays, but GCG was statistically less effective than EGCG in the FRAP assay. For EC and C, the latter had less anti-free radical activity in the DPPH assay, but in LDL oxidation and FRAP assays the antioxidant activity was similar. Oral and intravenous dosing of GTE-epimer mixture led to increase in total plasma antioxidant capacity in rats. In general, both epicatechins and epimers had low bioavailability (0.08-0.31) and most of the observed differences between epicatechins and their corresponding epimers were small, even if they were statistically significant in some cases. It was concluded that the epimerisation reaction occurring in manufacturing canned and bottled tea drinks would not significantly affect antioxidant activity and bioavailability of total tea polyphenols.

Animals↗

PubMed2004

Different role of nitric oxide and endothelium-derived hyperpolarizing factor in endothelium-dependent hyperpolarization and relaxation in porcine coronary arterial and venous system.

OBJECTIVE: We compared the basal and bradykinin (BK)-induced NO release and endothelium-derived hyperpolarizing factor-mediated function between coronary arteries and cardiac veins. METHODS AND RESULTS: Isolated coronary vessels (large arteries, cardiac veins as well as microvessels) were studied. An NO-specific electrode and a conventional intracellular glass microelectrode were used to directly measure NO released from endothelial cells and hyperpolarization of smooth muscle cells in conduit coronary vessels. The basal and BK-induced release of NO was 14.2 +/- 2.0 nmol/L and 237.1 +/- 27.2 nmol/L (n = 8) in the artery, significantly greater than in veins (8.0 +/- 1.1 nmol/L and 135.6 +/- 14.5 nmol/L, n = 8, P < 0.01). The BK-induced hyperpolarization was significantly reduced by N-nitro-L-arginine, indomethacin, and hemoglobin in both arteries and veins and was greater in the arteries. The EDHF-mediated relaxation was significantly higher in the arteries than in veins, greater in microveins than in large veins, and almost abolished by charybdotoxin and apamin. CONCLUSIONS: Both NO and EDHF are involved in the regulation of the vascular tone in the coronary arterial and venous systems but the amount of NO release and the EDHF-mediated relaxation and associated hyperpolarization are less significant in the vein than in the artery in the coronary system.

Animals↗

PubMed2004

Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain.

Protein glycosylation modifies the processing of several key proteins involved in the molecular pathogenesis of Alzheimer's disease (AD). Aberrant glycosylation of tau and down-regulation of sialyltransferase in AD brain suggest a possible dysregulation of protein glycosylation that may play a role in AD. We therefore isolated major glycoproteins from AD brain by using lectin-affinity chromatographies and ion-exchange chromatography and further separated them using SDS-polyacylamide gel electrophoresis. Mass spectrometry analysis of 11 isolated glycoproteins led to their identification as: neuronal cell adhesion molecule, beta-globin, IgM heavy chain VH1 region precursor, contactin precursor, dipeptidylpeptidase VI, CD81 partner 3, prenylcysteine lyase, adipocyte plasma-associated protein, acid ceramidase and two novel proteins. We found that the level and activity of acid ceramidase (AC), one of the major identified human brain glycoproteins, were significantly elevated in AD brain. Immunohistochemical staining indicated that AC was located mainly in the cell bodies of neurons and colocalized with neurofibrillary tangles. Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC-mediated signalling pathways might be involved in the molecular mechanism of AD.

Aged↗

PubMed2004

Urocortin and cardiovascular protection.

Urocortin and other hypothalamus corticotropin-releasing factor (CRF) polypeptides play biologically diverse roles in the stress, cardiovascular and inflammatory responses by acting on central and peripheral CRF receptors. Urocortin shows a significantly high sequence homology to CRF, and the concurrent expression of type-2 CRF (CRF2) receptors with urocortin in the heart suggests that urocortin may play a physiological role in the cardiac function. Urocortin is thought to be the endogenous agonist producing the cardiovascular actions previously attributed to CRF. This review highlights the current novel findings on the molecular and cellular mechanisms by which urocortin may exert its cardiovascular protective action.

Animals↗

PubMed2004

[Study on T cell subsets and their activated molecules from the convalescent SARS patients during two follow-up surveys].

AIM: To explore the changes of peripheral blood T cell subsets and their activated molecules in convalescent SARS patients. METHODS: In two follow-up surveys of the SARS patients discharged from our hospital, the changes of CD3(+), CD4(+), CD8(+), CD8(+) CD28(+), CD8(+) CD28(-), CD3(+) CD25(+), CD3(+) CD69(+), CD3(+) HLA-DR(+)T cells and the ratio of CD4(+)/CD8(+) T cells in peripheral blood of SARS patients treated unitedly with Chinese and Western medicines were detected by flow cytometry. RESULTS: In two follow-up surveys, the percentages of CD3(+), CD4(+), CD8(+) CD28(+) T cells and the ratio of CD4(+)/CD8(+) T cells were remarkably lower than those of normal values(P<0.05), while the percentage of CD8(+) CD28 (-) T cells was higher(P<0.01). As for the percentages of CD3(+), CD8(+), CD4(+)/CD8(+), CD3(+) CD25(+), CD3(+) CD69(+) and CD3(+) HLA-DR(+) T cells, there was marked difference between 1st and 2nd follow-up results, but for other molecules there was no notable difference. CONCLUSION: The convalescent SARS patients' immune function gradually recovers, and the effect of SARS virus on activation of T cells gradually disappears.

CD3 Complex↗