Biomedical subjects

Jie Liu

Publications and source records attributed to Jie Liu.

At least 217 records · Page 12Linked to original sources

PubMed2005

[Role of dendritic cells in the pathogenesis of allergic rhinitis in mouse].

OBJECTIVE: To investigate the role of dendritic cells in the pathogenesis of acute attack of allergic rhinitis in mouse. METHOD: The adherent precursors of DC were isolated from peripheral blood of allergic rhinitis mouse in acute attack stage and healthy controls. The adherent cells were induced with CpG ODN-1826 to DC in vitro. The expression of the surface molecules CD80, CD86, HLA-DR etc. on the DC was examined by fluorescent activated cell sorter (FACS), so the ability of DCs secrete IL-10, IL-12. RESULT: The results showed that the allergic rhinitis mouse in acute attack stage had remarkably decreased the ability to secret IL-10 compared with normal control subjects (P <0.01), while the ability to secret IL-12 remarkably decreased compared with normal control subjects (P < 0.01); meanwhile, the HLA-DR and co-stimulating factor CD86 expressed by DCs remarkably increased in the allergic rhinitis mouse in acute attack stage compared with the normal control subjects (P < 0.01). CONCLUSION: DC possibly plays a vital role in the immunological mechanism of allergic rhinitis by means of inducing the differentiation of Th1/Th2, that is DC may be the key factor in initiating the airway allergic reaction and the possible mechanism may involve interleukins (especially IL-10 and IL-12, etc.) secreted by DCs.

Animals↗

PubMed2005

[Expression of p21WAF1, p27KIP1 and cyclin E in ameloblastoma].

OBJECTIVE: To investigate the expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (AB), and to explore the clinical and biological characteristics of AB. METHODS: The expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human AB were detected by in situ hybridization or immunohistochemistry (SP method). RESULTS: The positive expression rate of cyclin E mRNA in the cytoplasm or cell nucleus of AB was 66.7% (36/54). The expression of cyclin E mRNA increased with AB recurrence and malignant transformation, and the difference of expression among primary AB, recurrent AB, and malignant AB, was statistically significant. The positive expression ratio of cyclin E mRNA in OKC was 50.0% (8/16). The p21(WAF1) mRNA expression in the cytoplasm or cell nucleus of AB decreased, and the positive ratio was 22.6% (12/54) in AB, 37.5% (6/16) in OKC, respectively. The p27(KIP1) protein expression in the cell nucleus of AB was positive in a small number of cases, and the positive rate was 16.7% (9/54) in AB, 6.3% (1/16) in OKC, respectively. CONCLUSIONS: The genesis and invasion of AB is associated with the cell proliferation and differentiation, and regulated by the higher expression of cyclin E and the lower expression of p21(WAF1) and p27(KIP1).

Adolescent↗

PubMed2005

[Retrospective observation of curative effects on MDS refractory anemia with combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen].

This study was aimed to examine whether a combination of all-trans retinoic acid (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail. 62 cases receiving a scheme of combination of ATRA, 1, 25-dihydroxyvitamin D(3) and androgen (group A) were monitored. The remaining 33 cases (group B) were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination. Bone marrow aspiration and biopsy were performed for collecting the specimens at the baseline and afterwards. The conditions of the patients were monitored by means of weekly complete blood counts and the monthly examination, including toxicity test, physical examination, electrocardiography, and biochemistry panel. The results showed that after treating for 8 weeks in group A, 4 out of 62 patients showed complete remission and 12 patients showed partial remission according to the defined response criteria, and 43 patients (69.35%) showed hematological improvement (HI). The further treatment for 16 out of 62 patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(5)) with a median survival interval of 26.25 months, were observed and interrupted for some reasons. However, partial remission was observed only in 3 patients in group B, and HI amounted to 51.51%. Furthermore, the disease progression was observed in 12 out of 33 patients (36.36%) with a median survival interval of 16 months, 9 failures (including 6 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)). The overall ratios of survival for 3 and 5 years in group A, which received the combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23% and 31.34% in the patients of group B (log-rank, P = 0.016). The following requirements, if were met, would be significant for prognosis: the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P < 0.05). Moreover, Cox regression showed that therapy, transformation and age are all the independent factors (P < 0.05). It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumor-promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.

Adolescent↗

PubMed2005

[Determination of copper, zinc, iron, calcium and magnesium in Pueraria lobata ohwi by FAAS].

The samples of Pueraria lobata ohwi were digested by HNO3 + HClO4. Copper, zinc, iron, calcium and magnesium in pueraria lobata ohwi from Da Bieshan were successfully determined by flame atomic absorption spectrophotometry (FAAS). The results showed that there are rich grand elements, such as Ca and Mg, and profitable elements, such as trace elements Cu, Zn and Fe, in Pueraria lobata ohwi. The content sequence of metal elements is as follows: Copper: leaves > flowers > rattans > roots; Zinc: leaves > flowers > rattans > roots; Iron: roots > rattans > leaves > flowers; Calcium: leaves > roots > flowers > rattans; Magnesium: flowers > roots > leaves > rattans. The results provided useful data for discussing the relationship between the metal elements in Pueraria lobata and hypertension diseases. ohwi and the cure for cerebrovascular diseases.

Calcium↗

PubMed2005

[Impact of macrofaunal activities on the DIN exchange at the sediment-water interface along the tidal flat of Yangtze River estuary].

The macrofaunal activities exert intensive and extensive influences on the accumulation, transportation, exchange and geochemistry processes of pollutants and redox sensitive elements around the sediment-water interface. Based on the simulated and contrastive analysis method, effects of bivalve Corbicula fluminea activities on dissolved inorganic nitrogen (DIN) exchange between sediment-water interface in different experimental conditions and nitrogen biogeochemical cycling along the tidal flats of Yangtze River estuary are discussed. In short time experiment, Corbicula fluminea burrowing activities increased NH4+ release from sediments, and NO3- efflux to overlying water was much more in Corbicula fluminea inhabiting core. During long time incubation, NH4- and N released in turn from the sediments, bioturation can facilitate NH4- release from the sediments at the beginning of incubation, and stronger nmistrification derived from bioturbation witin the sediments enlarge Nsedim concentration. Disturbance and bioirrigation of Corbicula flumuminea can accelerate organic matter mineralization and N(DIN) exchange between overlying water and pore water, result in a larger release from NH4+ pool in top-sediment to overlying water. In conclusion, by means of excretion, burrowing, bioirrigation and biotuary ation, Corbicula fluuminea burrowing activities can evidently modify the nitrogen dynamics in sediment-water system.

Animals↗

PubMed2005

[Determination of polysaccharide from Chinese medicine Morinda officinalis how and its trace elements analysis].

Polysaccharide was extracted from morinda officinalis how by back-flowing with 80% ethanol for 1 h, and the method of improved phenol-sulfuric acid spectroscopy was adopted to determine the content of morinda officinalis how polysaccharide. As for its trace elements, the atomic absorption spectroscopy was used to detect the content of Zn, Fe and Cu, which were compared with its fake; and cold atomic fluorometry was applied to determine the trace mercury. The results were satisfactory, which can give reference about the effective components of morinda officinalis how, and will help to exploit it.

Copper↗

PubMed2004

Cadmium at a non-toxic dose alters gene expression in mouse testes.

The testes are important targets of cadmium (Cd)-induced toxicity and carcinogenicity in rodents. Exposure to Cd at environmentally relevant low levels is a significant human health concern, but the effects of Cd on the rodent testes at doses that do not cause overt lesions are poorly defined. We used cDNA microarray and quantitative real-time RT-PCR assays to determine gene expression profiles in the testes of CD-1 mice 12-72 h after a single s.c. injection of 5 micromol/kg CdCl2. This dose of Cd did not produce overt histopathological changes, but clearly altered the expression of some genes that are likely to be important in toxicity responses. The most significant changes in gene expression occurred 24 h after treatment, corresponding to when the highest level of Cd was detected in the testes. Increased expression of the C-myc and Egr1 genes strongly suggests acute stress responses. Repressed expression of cell cycle-regulated cyclin B1 and CDC2 proteins indicates a potential for causing G2/M arrest and disturbance of meiosis. Decreased expression of pro-apoptotic genes, particularly Casp3, and DNA repair genes possibly contributes to Cd-induced carcinogenesis. These results indicate that changes in gene expression occur well before overt effects of Cd-induced testicular toxicity and carcinogenicity are apparent.

Animals↗

PubMed2004

3-hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity.

The purpose of this study was to develop a novel therapy for Parkinson's disease (PD). We recently reported that dextromethorphan (DM), an active ingredient in a variety of widely used anticough remedies, protected dopaminergic neurons in rat primary mesencephalic neuron-glia cultures against lipopolysaccharide (LPS)-mediated degeneration and provided potent protection for dopaminergic neurons in a MPTP mouse model. The underlying mechanism for the protective effect of DM was attributed to its anti-inflammatory activity through inhibition of microglia activation. In an effort to develop more potent compounds for the treatment of PD, we have screened a series of analogs of DM, and 3-hydroxymorphinan (3-HM) emerged as a promising candidate for this purpose. Our study using primary mesencephalic neuron-glia cultures showed that 3-HM provided more potent neuroprotection against LPS-induced dopaminergic neurotoxicity than its parent compound. The higher potency of 3-HM was attributed to its neurotrophic effect in addition to the anti-inflammatory effect shared by both DM and 3-HM. First, we showed that 3-HM exerted potent neuroprotective and neurotrophic effects on dopaminergic neurons in rat primary mesencephalic neuron-glia cultures treated with LPS. The neurotrophic effect of 3-HM was glia-dependent since 3-HM failed to show any protective effect in the neuron-enriched cultures. We subsequently demonstrated that it was the astroglia, not the microglia, that contributed to the neurotrophic effect of 3-HM. This conclusion was based on the reconstitution studies, in which we added different percentages of microglia (10-20%) or astroglia (40-50%) back to the neuron-enriched cultures and found that 3-HM was neurotrophic after the addition of astroglia, but not microglia. Furthermore, 3-HM-treated astroglia-derived conditioned media exerted a significant neurotrophic effect on dopaminergic neurons. It appeared likely that 3-HM caused the release of neurotrophic factor(s) from astroglia, which in turn was responsible for the neurotrophic effect. Second, the anti-inflammatory mechanism was also important for the neuroprotective activity of 3-HM because the more microglia were added back to the neuron-enriched cultures, the more significant neuroprotective effect was observed. The anti-inflammatory mechanism of 3-HM was attributed to its inhibition of LPS-induced production of an array of pro-inflammatory and neurotoxic factors, including nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and reactive oxygen species (ROS). In conclusion, this study showed that 3-HM exerted potent neuroprotection by acting on two different targets: a neurotrophic effect mediated by astroglia and an anti-inflammatory effect mediated by the inhibition of microglial activation. 3-HM thus possesses these two important features necessary for an effective neuroprotective agent. In view of the well-documented very low toxicity of DM and its analogs, this report may provide an important new direction for the development of therapeutic interventions for inflammation-related diseases such as PD.

Animals↗

PubMed2004

Expression and significances of Id1 helix-loop-helix protein overexpression in gastric cancer.

The Id family of helix-loop-helix proteins is involved in a variety of biological processes, including development,proliferation, and angiogenesis. There is emerging evidence for deregulation of Id proteins in some cancers. Hence we determined Id expression in gastric cancer. To elucidate the involvement of Idl in gastric carcinogenesis, Immunohistochemistry was carried out on paraffin-embedded gastric cancer sections. By analyzing the relationship between the Idl staining index of individual tumors and the patient's clinical parameters, including histological grade, clinical stage, and presence of metastases, we found that strong Idl expression was associated with poorer differentiation and more aggressive behavior of tumor cells. To further explore Idl expression in human gastric carcinomas, Western blot analysis was performed to analyze Idl protein expression in 15 pairs of gastric tissues and cancers and in gastric cell lines. Idl was found to be expressed at higher levels in 11/15 cancer tissues compared to adjacent tissues. Idl was upregulated more prominently in the poorly differentiated cell lines than in the well-differentiated ones. Semiquantitative RT-PCR was carried out to investigate the expression of mRNA of Idl in gastric cancer cell lines and it was upregulated in most of them. Our results demonstrate that Idl protein may play an important role in the process of gastric carcinogenesis and high-level Id I expression may be related to the malignant potential of tumor cells.

Adult↗

PubMed2004

Constitutive expression of peroxisome proliferator-activated receptor alpha-regulated genes in dwarf mice.

Defects in growth hormone secretion or signaling in mice are associated with decreased body weights (dwarfism), increased longevity, increased resistance to stress, and decreases in factors that contribute to cardiovascular disease and cancer. Peroxisome proliferators (PP) alter a subset of these changes in wild-type mice through activation of the nuclear receptor family member PP-activated receptor alpha (PPARalpha). We tested the hypothesis that an overlap in the transcriptional programs between untreated dwarf mice and PP-treated wild-type mice underlies these similarities. Using transcript profiling, we observed a statistically significant overlap in the expression of genes differentially regulated in control Snell dwarf mice (Pit-1dw) compared with phenotypically normal heterozygote (+/dw) control mice and those altered by the PP 4-chloro-6-(2,3-xylidino)-2-pyrimidinyl)thioacetic acid (WY-14,643) in +/dw mice. The genes included those involved in beta- and omega-oxidation of fatty acids (Acox1, Cyp4a10, Cyp4a14) and those involved in stress responses (the chaperonin, T-complex protein1epsilon) and cardiovascular disease (fibrinogen). The levels of some of these gene products were also altered in other dwarf mouse models, including Ames, Little, and growth hormone receptor-null mice. The constitutive increases in PPARalpha-regulated genes may be partly caused by increased expression of PPARalpha mRNA and protein as observed in the livers of control Snell dwarf mice. These results indicate that some of the beneficial effects associated with the dwarf phenotype may be caused by constitutive activation of PPARalpha and regulated genes.

Animals↗

PubMed2004

Minimal influence of metallothionein over-expression on nickel carcinogenesis in mice.

Metallothionein (MT) is a metal-binding protein associated with tolerance to metals and oxidative stress. Nickel is a metal carcinogen potentially acting through oxidative attack on critical biomolecules. We investigated the role of MT in nickel carcinogenesis using MT-transgenic mice that constitutively over-express MT-I in all tissues tested. Groups of 25 male MT-transgenic and wild type (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni3S2) in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age and were observed for 104 weeks. Injection site tumors (ISTs; primarily fibrosarcomas) started occurring 45 weeks after nickel injection and IST incidence was similar in the WT (control - 0%, 0.5 mg/site - 20%, 1.0 mg/site - 40%) and MT-transgenic mice (control - 0%, 0.5mg/site - 28%, 1.0mg/site - 29%.). At the 0.5 mg/site dose the average time to IST in MT-transgenic mice was approximately 13 weeks shorter than in WT mice. Spontaneous lung tumors developed in 25% of control WT mice but none developed in control MT-transgenic mice. A nickel dose-related trend for increased lung tumors occurred in MT-transgenic mice but not in WT mice. Thus, the over-expression of MT did not significantly mitigate the carcinogenic response to nickel.

Acid Anhydride Hydrolases↗

PubMed2004

Protective effect of dextromethorphan against endotoxic shock in mice.

Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 h after an injection of LPS/GalN (20 microg/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis.

Animals↗

PubMed2004

Gating charges in the activation and inactivation processes of the HERG channel.

The hERG channel has a relatively slow activation process but an extremely fast and voltage-sensitive inactivation process. Direct measurement of hERG's gating current (Piper, D.R., A. Varghese, M.C. Sanguinetti, and M. Tristani-Firouzi. 2003. PNAS. 100:10534-10539) reveals two kinetic components of gating charge transfer that may originate from two channel domains. This study is designed to address three questions: (1) which of the six positive charges in hERG's major voltage sensor, S4, are responsible for gating charge transfer during activation, (2) whether a negative charge in the cytoplasmic half of S2 (D466) also contributes to gating charge transfer, and (3) whether S4 serves as the sole voltage sensor for hERG inactivation. We individually mutate S4's positive charges and D466 to cysteine, and examine (a) effects of mutations on the number of equivalent gating charges transferred during activation (z(a)) and inactivation (z(i)), and (b) sidedness and state dependence of accessibility of introduced cysteine side chains to a membrane-impermeable thiol-modifying reagent (MTSET). Neutralizing the outer three positive charges in S4 and D466 in S2 reduces z(a), and cysteine side chains introduced into these positions experience state-dependent changes in MTSET accessibility. On the other hand, neutralizing the inner three positive charges in S4 does not affect z(a). None of the charge mutations affect z(i). We propose that the scheme of gating charge transfer during hERG's activation process is similar to that described for the Shaker channel, although hERG has less gating charge in its S4 than in Shaker. Furthermore, channel domain other than S4 contributes to gating charge involved in hERG's inactivation process.

Amino Acid Substitution↗

PubMed2004

Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB.

Pseudohypoparathyroidism type IB (PHPIB) is associated with abnormal imprinting of GNAS, the gene encoding the heterotrimeric G protein Gsalpha and other alternative products. The gene contains three differentially methylated regions (DMRs) located upstream of the Gsalpha promoter (from upstream to downstream): the paternally methylated NESP55 promoter region, the maternally methylated NESP antisense (NESPAS)/XLalphas promoter region and the maternally methylated exon 1A region located just upstream of the Gsalpha promoter. We have now performed a detailed analysis of the GNAS methylation profile in 20 unrelated PHPIB probands. Consistent with prior results, all have loss of exon 1A imprinting (a paternal epigenotype on both alleles). All five probands with familial disease had a deletion mutation within the closely linked STX16 gene and a GNAS imprinting defect involving only the exon 1A region. In contrast, the STX16 mutation was absent in all sporadic cases. The majority of these patients had abnormal imprinting of the more upstream regions in addition to the exon 1A imprinting defect, with eight of 15 having a paternal epigenotype on both alleles throughout the GNAS locus. In virtually all cases, the imprinting status of the NESP55 and NESPAS/XLalphas promoters is concordant, suggesting that their imprinting is co-regulated, whereas the imprinting of the NESPAS/XLalphas promoter region and XLalphas first exon is not always concordant even though they are closely linked and lie within the same DMR. Familial and sporadic forms of PHPIB have distinct GNAS imprinting patterns that occur through different defects in the imprinting mechanism.

Alleles↗

PubMed2004

Atomic structure of a tryptophan-zipper pentamer.

Coiled-coil motifs are ubiquitous mediators of specific protein-protein interactions through the formation of interlocking hydrophobic seams between alpha-helical chains. Residues that form these seams occur at the first (a) and fourth (d) positions of a characteristic 7-aa repeat and are primarily aliphatic. The potential of aromatic residues to promote helix association in a coiled coil was explored by engineering a "Trp-zipper" protein with Trp residues at all 14 a and d positions. The protein forms a discrete, stable, alpha-helical pentamer in water at physiological pH. Its 1.45-A crystal structure reveals a parallel, five-stranded coiled coil, a previously uncharacterized type of "knobs-into-holes" packing interaction between interfacial Trp side chains, and an unusual approximately 8-A-diameter axial channel lined with indole rings that is filled with polyethylene glycol 400 and water and sulfate ion molecules. The engineered Trp-zipper pentamer enlarges current views of coiled-coil assembly, molecular recognition, and protein engineering, and may serve as a soluble model for membrane ion channels.

Amino Acid Motifs↗

PubMed2004

Metallothionein-I/II double knockout mice are hypersensitive to lead-induced kidney carcinogenesis: role of inclusion body formation.

Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead toxicity, and were sensitive to the subchronic toxic effects of lead exposure (10 weeks), showing modestly diminished renal function and nephromegaly compared with wild-type (WT) mice. It is unclear how this knockout might impact lead carcinogenesis. Thus, the effects of lead(II) acetate were tested in groups (n = 25) of male metallothionein-null and WT mice receiving drinking water with 0, 1,000, 2,000, or 4,000 parts per million lead for up to 104 weeks. Renal proliferative lesions (adenoma and cystic tubular atypical hyperplasia) were much more common and more severe in lead-exposed metallothionein-null mice than in WT mice. A metastatic renal cell carcinoma also occurred in a lead-treated metallothionein-null mouse, whereas none occurred in WT mice. Lead-induced renal proliferative lesions showed marked overexpression of cyclin D1, a common feature of human renal tumors. Renal lead-containing nuclear inclusion bodies were frequently observed in WT mice but did not form in metallothionein-null mice. Metallothionein was often found associated with the outer portion of these inclusion bodies. Thus, the metallothionein-null mice cannot form renal inclusion bodies, even after protracted lead exposure, and this increases the carcinogenic potential of lead. Poor production of metallothionein may predispose human populations to lead carcinogenicity.

Animals↗

PubMed2004

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart.

Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle (C(t)) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Nav beta 1, Nav beta 3, Cav1.3, Cav3.1 and Cav alpha 2 delta 2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cav beta 2 and Cav gamma 4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvbeta1, MinK and Cav gamma 7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.

Animals↗

PubMed2004

Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension.

BACKGROUND: Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension. METHODS AND RESULTS: In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB1) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats. CONCLUSIONS: We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension.

Amidohydrolases↗