Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 195
Filter
1.
Article in Chinese | WPRIM | ID: wpr-826691

ABSTRACT

OBJECTIVE@#To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke.@*METHODS@#A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups.@*RESULTS@#After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (<0.01) and CSS score decreased as compared with that before treatment (<0.01). After treatment, FMA score in the observation group was higher than that in the control group (<0.01) and CSS score was lower than the control group (<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (<0.01) and that of cGMP decreased as compared with that before treatment (<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (<0.01) and that of cGMP was lower than the control group (<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (<0.01).@*CONCLUSION@#The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Brain Ischemia , Therapeutics , Cyclic AMP , Blood , Cyclic GMP , Blood , Hemiplegia , Therapeutics , Humans , Stroke , Therapeutics , Stroke Rehabilitation , Treatment Outcome
2.
Bol. latinoam. Caribe plantas med. aromát ; 19(6): 555-568, 2020. tab, ilus
Article in English | LILACS | ID: biblio-1284299

ABSTRACT

Despite the development of modern medicine, alternative medicine, which has not lost its timeliness, remains attractive for the treatment of various diseases. Glabridin, a major flavonoid of Glycyrrhiza glabra, is known for its antioxidant and anti-inflammatory activity. The aim of this study was: 1) to determine the possible protective role of glabridin against ischemia/reperfusion (I/R) injury of the intestine; 2) to evaluate the in vitrocontractile responses of ileum smooth muscles to acetylcholine after an intestinal I/R; and 3) to explain the underlying molecular mechanism of its effect. Rats were assigned to groups of six rats each; 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester monohydrochloride (L-NAME)+gla40, and 6) Sham group. The healing effect of glabridin was abolished by L-NAME. Glabridin did not cause contractility of the smooth muscles to acetylcholine-induced contractile responses in intestinal I/R. Yet, it increased to spontaneous basal activity.


A pesar del desarrollo de la medicina moderna, la medicina alternativa, sin perder su vigencia, sigue siendo atractiva para el tratamiento de varias enfermedades. Glabradina, el flavonoide mayoritario de Glycyrrhiza glabra, es conocido por su actividad antioxidante y antiinflamatoria. Los propósitos de este estudio fueron: 1) Determinar el posible rol protector de glabradina ante daños intestinales por isquemia/reperfusion (I/R) 2) Evaluar in vitrolas respuestas de contracción de los músculos lisos del ileum ante acetilcolina después de I/R intestinal; y 3) Explicar el mecanismo molecular subyacente de este efecto. Se asignaron grupos de seis ratas: 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)metil]-L-ornithina, metil ester monohidrochloruro (L-NAME)+gla40, y 6) Grupo testigo. El efecto curativo de glabridina fue abolido por L-NAME. Glabridina no causó contracción en el músculo liso como respuesta acetilcolina-inducida I/R. Además, incrementa la actividad basal expontánea.


Subject(s)
Animals , Rats , Phenols/administration & dosage , Reperfusion Injury/drug therapy , Cyclic AMP/metabolism , Glycyrrhiza , Isoflavones/administration & dosage , Phenols/pharmacology , Rats, Wistar , Cyclic AMP/analysis , Cyclic GMP/metabolism , Oxidative Stress/drug effects , NG-Nitroarginine Methyl Ester , Ileum/drug effects , Ileum/chemistry , Isoflavones/pharmacology , Malondialdehyde/analysis , Muscle, Smooth/drug effects
3.
Braz. j. med. biol. res ; 53(3): e8853, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089343

ABSTRACT

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.


Subject(s)
Animals , Male , Rats , Cyclic GMP/antagonists & inhibitors , Enzyme Inhibitors/administration & dosage , Anaphylaxis/drug therapy , Muscle, Smooth, Vascular/drug effects , Nitric Oxide/antagonists & inhibitors , Rats, Wistar , NG-Nitroarginine Methyl Ester/administration & dosage , Disease Models, Animal , Indigo Carmine/administration & dosage , Methylene Blue/administration & dosage
4.
Rev. bras. oftalmol ; 78(1): 70-73, jan.-fev. 2019.
Article in Portuguese | LILACS | ID: biblio-1042373

ABSTRACT

Resumo O oxido nitrico (NO) é um fator relaxante derivado do endotélio e um potente vasodilatador que impacta em vários sistemas em todo o corpo. Estudos comprovam que o fluxo sanguíneo ocular basal é regulado pelo NO, sendo um importante regulador da homeostase, especialmente dentro dos tecidos uveais. A disfunção da produção de NO seria associado ao glaucoma através da alteração da perfusão da cabeça do nervo óptico associado ao aumento da pressão intraocular devido um sistema de drenagem trabecular deficiente. O NO tornou-se uma molécula atraente para o tratamento do glaucoma devido a possibilidade de modulação da drenagem trabecular, abaixando a pressão intraocular e ação neuroprotetora melhorando a perfusão sanguínea na cabeça do nervo óptico.


Abstract Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve.


Subject(s)
Glaucoma/metabolism , Nitric Oxide/metabolism , Ophthalmic Solutions , Trabecular Meshwork/metabolism , Glaucoma/drug therapy , Cyclic GMP/blood , Nitric Oxide Donors/therapeutic use , Latanoprost/therapeutic use , Intraocular Pressure , Antihypertensive Agents/therapeutic use
5.
Chinese Journal of Biotechnology ; (12): 558-566, 2019.
Article in Chinese | WPRIM | ID: wpr-771353

ABSTRACT

Bacterial biofilm refers to a tunicate-like biological group composed of polysaccharide, protein and nucleic acid secreted by bacteria on the surface of the mucous membrane or biological material. The biofilm formation is a major cause of chronic infections. Bacteria could produce some secondary metabolites during the growth and reproduction. Some of them act as signaling molecules allowing bacteria to communicate and regulate many important physiological behaviors at multiple-cell level, such as bioluminescence, biofilm formation, motility and lifestyles. Usually, these signal molecules play an important role in the formation of bacterial biofilm. We review here the effects of related signal molecules of Quorum Sensing, cyclic diguanylate, Two-Component Systems and sRNA on the biofilm formation. Focusing on these regulation mechanism of signal molecules in the process of biofilm formation is necessary for the prevention and treatment of some chronic diseases.


Subject(s)
Bacterial Proteins , Biofilms , Cyclic GMP , Gene Expression Regulation, Bacterial , Protein Binding , Quorum Sensing
6.
Article in English | WPRIM | ID: wpr-760060

ABSTRACT

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.


Subject(s)
Adenosine , Blotting, Western , Cyclic GMP , Dipyridamole , Humans , Matrix Metalloproteinases , Nitric Oxide , Permeability , Phosphodiesterase Inhibitors , Theophylline , Trabecular Meshwork
7.
Bol. latinoam. Caribe plantas med. aromát ; 17(3): 310-323, mayo 2018. ilus, tab
Article in English | LILACS | ID: biblio-915411

ABSTRACT

The aim of current study was to determinate ex vivo and chromatographic fingerprint by HPLC of four extracts of Euphorbia furcillata K. Ethyl acetate extract of Euphorbia furcillata (EaEEf) was the most effective and potent extract (Emax=98.69±1.24%) and its effect was partially endothelium-dependent. Functional vasorelaxant mechanism of action of EaEEf was determinate, EaEEf showed efficient relaxation of KCl [80 mM]-induced contraction and norepinephrine and CaCl2 contraction curves showed diminution of maximal contraction in the presence of EAEEf and EaEEf-relaxation curve was shifted to the right in the presence of L-NAME (nitric oxide synthase inhibitor) and ODQ (guanylate cyclase inhibitor). Chromatographic fingerprints analysis suggests presence of diterpenoid such as abietane, tigliane, and ingenane skeletons. Our experiments suggest the EaEEf vasorelaxant activity could be attributed to diterpenoid molecules whose mechanism involves nitric oxide production and calcium channel blockade.


Se determinó el efecto vasorrelajante ex vivo y los perfiles cromatográficos mediante HPLC de cuatro extractos de Euphorbia furcillata K.. El extracto de acetato de etilo de E. furcillata (EaEEf) fue el más eficaz y potente en la contracción inducida por norepinefrina (Emax=98.69±1.24%) y el efecto fue parcialmente dependiente del endotelio vascular. Se determinó el mecanismo de acción vasorrelajante para EaEEf, este mostró ser eficaz sobre la contracción inducida por KCl [80 mM] y la curva de contracción en respuesta a norepinefrina y CaCl2 en presencia de EaEEf mostró disminución en la contracción máxima, mientras que la curva de relajación de EaEEf en presencia de L-NAME (inhibidor de óxido nítrico sintasa) y ODQ (inhibidor de guanilato ciclasa) se desplazó hacia la derecha. El análisis cromatográfico de EaEEf sugiere la presencia de moléculas diterpenoides como abietano, tigliano y esqueletos de ingenano. Nuestros resultados sugieren que el efecto vasorrelajante de EaEEf podría atribuirse a moléculas diterpenoides, cuyo mecanismo de acción involucra la producción de óxido nítrico y bloqueo de canales de calcio.


Subject(s)
Animals , Male , Rats , Vasodilator Agents/pharmacology , Plant Extracts/pharmacology , Euphorbia/chemistry , Calcium Channel Blockers/metabolism , Chromatography, High Pressure Liquid , Rats, Wistar , Cyclic GMP/metabolism , Nitric Oxide/metabolism
8.
Article in English | WPRIM | ID: wpr-691364

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.</p><p><b>METHODS</b>The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen (PCNA) and smooth muscle (SM) α-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 (ERK2), MAPK phosphatase-1 (MKP-1) and endothelial nitric oxide synthase (eNOS) were determined by real-time reverse transcription-polymerase chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. The plasma contents of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) were also determined.</p><p><b>RESULTS</b>Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury (P<0.05 or P<0.01). The positive expression rate of PCNA was decreased, while the expression rate of SM α-actin obviously increased in the vascular wall after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01). Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated (P<0.05 or P<0.01). The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downregulated after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01), respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.</p>


Subject(s)
Actins , Metabolism , Animals , Carotid Arteries , Metabolism , Pathology , Carotid Artery Injuries , Drug Therapy , Genetics , Pathology , Cyclic GMP , Blood , Disease Models, Animal , Gene Expression Regulation , Hyperplasia , Indole Alkaloids , Pharmacology , Therapeutic Uses , Male , Nitric Oxide , Blood , Phosphorylation , Proliferating Cell Nuclear Antigen , Metabolism , Quinazolines , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Tunica Intima , Pathology
9.
Article in English | WPRIM | ID: wpr-687928

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.</p><p><b>METHODS</b>The ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.</p><p><b>RESULTS</b>Preconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.</p><p><b>CONCLUSION</b>BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.</p>


Subject(s)
Animals , Area Under Curve , Berberis , Chemistry , Blood Pressure , Cyclic GMP , Metabolism , Epoprostenol , Pharmacology , In Vitro Techniques , Indomethacin , Pharmacology , Male , Models, Biological , Muscle Relaxation , Muscle, Smooth , Physiology , NG-Nitroarginine Methyl Ester , Pharmacology , Nitric Oxide , Metabolism , Penile Erection , Phenylephrine , Pharmacology , Plant Extracts , Pharmacology , Potassium Channel Blockers , Pharmacology , Potassium Channels , Metabolism , Pressure , Rabbits
10.
Braz. j. med. biol. res ; 51(5): e6714, 2018. tab, graf
Article in English | LILACS | ID: biblio-889083

ABSTRACT

This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR) control group received DMSO (1 µL/kg) immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg) were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg) and LY294002 (10 µM), L-NAME (10 μM), or norbinaltorphimine (norBIN, 1 μM) after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF) were also measured. The phosphorylation of AKT (p-AKT) was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE) and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.


Subject(s)
Animals , Male , Rats , Cerebral Arteries/drug effects , Brain Ischemia/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Diterpenes, Clerodane/pharmacology , Signal Transduction , Cerebral Arteries/physiopathology , Brain Ischemia/drug therapy , Morpholines/administration & dosage , Chromones/administration & dosage , Rats, Sprague-Dawley , Cyclic GMP/cerebrospinal fluid , Cyclic GMP/metabolism , NG-Nitroarginine Methyl Ester , Diterpenes, Clerodane/antagonists & inhibitors , Disease Models, Animal , Naltrexone/administration & dosage , Naltrexone/analogs & derivatives
11.
Braz. j. med. biol. res ; 51(5): e6693, 2018. graf
Article in English | LILACS | ID: biblio-889091

ABSTRACT

Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice. For this purpose, we recorded ATP-evoked currents in isolated Leydig cells using the whole cell patch clamp technique after treatment with L-NAME (300 μM and 1 mM), L-arginine (10, 100, 300, and 500 μM), ODQ (300 μM), and 8-Br-cGMP (100 μM). Our results show that NO produced by Leydig cells in basal conditions is insufficient to change the ATP-evoked currents and that extra NO provided by adding 300 μM L-arginine positively modulates the current through a mechanism involving the NO/cGMP signaling pathway. Thus, we report an interaction between the nitrergic and purinergic systems in Leydig cells and suggest that Ca2+ entry via the purinergic receptors can be regulated by NO.


Subject(s)
Animals , Male , Mice , Adenosine Triphosphate/physiology , Receptors, Purinergic/metabolism , Leydig Cells/physiology , Nitric Oxide/physiology , Arginine/administration & dosage , Arginine/metabolism , Thionucleotides/administration & dosage , Thionucleotides/metabolism , Action Potentials , Cells, Cultured , Cyclic GMP/administration & dosage , Cyclic GMP/analogs & derivatives , Cyclic GMP/metabolism , Patch-Clamp Techniques , NG-Nitroarginine Methyl Ester/administration & dosage , NG-Nitroarginine Methyl Ester/metabolism , Nitric Oxide/biosynthesis
13.
Motriz (Online) ; 23(1): 1-6, Jan.-Mar. 2017. tab, ilus
Article in English | LILACS | ID: biblio-841831

ABSTRACT

Abstract The second messenger cGMP has been largely studied as a therapeutic target in a variety of disorders such as erectile dysfunction, arterial hypertension and heart failure. Evidence has shown thatcGMP activators are less efficient in estrogen-deficiency animals, but no studies exist involving non-pharmacological approacheson NO/cGMP signaling pathway in hypertensive postmenopausal women. The aim of this study is to examine NO/cGMP pathway, redox state and blood pressure in trained treatedhypertensive (HT) postmenopausal women comparing with normotensive (NT) group. The rationale for that is most of HT patients is encouraged by physician to perform exercise associated with pharmacological treatments.Aerobic exercise training (AET) consisted of 24 sessions, 3 times/week.Parameters were evaluated at baseline and after AET for both groups (HT=28; NT=33).In treatedHT group, AET was significantly effective in increasing cGMP concentrations (28%) accompanied by an up-regulation of SOD (97%) and catalase activity (37%). In NT group, we found an increasein SOD activity (58%). TreatedHT postmenopausal women were still responsive to AET increasing cGMP levels and up-regulating antioxidant system. It should also be emphasized that these findings provide information on the circulating biomarkers that might delay the developing of cardiovascular events in this particular population.(AU)


Subject(s)
Humans , Female , Middle Aged , Aged , Cyclic GMP/metabolism , Exercise , Hypertension , Postmenopause/physiology
14.
Protein & Cell ; (12): 83-89, 2017.
Article in English | WPRIM | ID: wpr-757392

ABSTRACT

RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box helicases comprise the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recent literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41. After bacterial or viral infection, DNA or cyclic-di-GMP is released to cells. After phosphorylation of Tyr414 by BTK kinase, DDX41 will act as a sensor to recognize the invaders, followed by induction of type I interferons (IFN). After the immune response, DDX41 is degraded by the E3 ligase TRIM21, using Lys9 and Lys115 of DDX41 as the ubiquitination sites. Besides the roles in innate immunity, DDX41 is also related to diseases. An increasing number of both inherited and acquired mutations in DDX41 gene are identified from myelodysplastic syndrome and/or acute myeloid leukemia (MDS/AML) patients. The review focuses on DDX41, as well as its homolog Abstrakt in Drosophila, which is important for survival at all stages throughout the life cycle of the fly.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase , Animals , Bacterial Infections , Genetics , Allergy and Immunology , Cyclic GMP , Genetics , Allergy and Immunology , DEAD-box RNA Helicases , Genetics , Allergy and Immunology , Drosophila Proteins , Genetics , Allergy and Immunology , Drosophila melanogaster , Humans , Leukemia, Myeloid, Acute , Genetics , Allergy and Immunology , Mutation , Myelodysplastic Syndromes , Genetics , Allergy and Immunology , Nuclear Proteins , Genetics , Allergy and Immunology , Protein-Tyrosine Kinases , Genetics , Allergy and Immunology , Virus Diseases , Genetics , Allergy and Immunology
15.
Protein & Cell ; (12): 403-416, 2016.
Article in English | WPRIM | ID: wpr-757127

ABSTRACT

YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the periplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal structures of YfiB alone and of an active mutant YfiB(L43P) complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiB(L43P) adopts a stretched conformation allowing activated YfiB to penetrate the peptidoglycan (PG) layer and access YfiR. YfiB(L43P) shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YfiB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YfiR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiB(L43P)-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system.


Subject(s)
Amino Acid Sequence , Bacterial Proteins , Chemistry , Genetics , Metabolism , Binding Sites , Biofilms , Crystallography, X-Ray , Cyclic GMP , Metabolism , Dimerization , Molecular Dynamics Simulation , Molecular Sequence Data , Mutagenesis , Protein Structure, Quaternary , Pseudomonas aeruginosa , Metabolism , Sequence Alignment , Tryptophan , Chemistry , Metabolism , Vitamin B 6 , Chemistry , Metabolism
16.
Acta Physiologica Sinica ; (6): 329-334, 2015.
Article in Chinese | WPRIM | ID: wpr-255942

ABSTRACT

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.


Subject(s)
Animals , Basilar Artery , Blood Pressure , Cerebral Arteries , Chalcones , Pharmacology , Cyclic GMP , Physiology , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Physiology , Patch-Clamp Techniques , Potassium Channels, Calcium-Activated , Physiology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Systole
17.
Acta Physiologica Sinica ; (6): 497-504, 2015.
Article in Chinese | WPRIM | ID: wpr-255920

ABSTRACT

The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.


Subject(s)
Animals , Brain Stem , Chemistry , Cerebral Cortex , Chemistry , Cyclic AMP , Chemistry , Cyclic GMP , Chemistry , Formaldehyde , Toxicity , Hippocampus , Chemistry , Male , Mice , Mice, Inbred BALB C , Nitric Oxide , Chemistry , Nitric Oxide Synthase , omega-N-Methylarginine , Pharmacology
18.
Article in Chinese | WPRIM | ID: wpr-255174

ABSTRACT

<p><b>OBJECTIVE</b>To prepare rabbit monoclonal antibody (RabMab) against guanosine 3', 5'-cyclic monophosphate (cGMP) and to develop a competitive ELISA for the detection of cGMP.</p><p><b>METHODS</b>New Zealand white rabbits were immunized with synthesized cGMP-keyhole limpet hemoeyanin (cGMP-KLH) to prepared a RabMAb with monoclonal antibody technique of Epitomics. A competitive ELISA kit was produced with cGMP RabMAb. The specificity, the precision and the recoveries of the method were determined.</p><p><b>RESULTS</b>The RabMAb with high sensitivity towards cGMP were prepared with an antibody timer of 3.1 ng/mL and 50% inhibitive concentration (IC50) of 12.57 ng/mL. The cGMP RabMAb had 33% cross-reactivity to inosine 3', 5'-cyclic monophosphate (cIMP) and little or no cross-reactivity to other compounds. A competitive ELISA was developed for detection of cGMP. The range of detection was 0~120 ng/mL with a minimal limit of 1.95 ng/mL. The recovery of assay was 89%~103%. The inter-assay and intra-assay coefficient variations were below 11.68% and 13.85%, respectively.</p><p><b>CONCLUSION</b>The RabMab against cGMP with high affinity and high specificity has been generated successfully, and a competitive ELISA for detection of cGMP has been developed with the prepared cGMP RabMAb.</p>


Subject(s)
Animals , Antibodies, Monoclonal , Antibody Specificity , Cross Reactions , Cyclic GMP , Allergy and Immunology , Enzyme-Linked Immunosorbent Assay , Rabbits
19.
Article in English | WPRIM | ID: wpr-812148

ABSTRACT

Scutellarin (SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction (ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and -independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU (10-1 000 μmol·L(-1)) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-cGMPS (PKGI-rp, 4 μmol·L(-1)), significantly blocked SCU (10-1 000 μmol·L(-1))-induced relaxation. The NO synthase (NOS) inhibitor, NO-nitro-L-arginine methylester (L-NAME, 100 μmol·L(-1)), did not significantly change the effects of SCU (10-1 000 μmol·L(-1)). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU (500 μmol·L(-1)), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp (4 μmol·L(-1)) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein (p-VASP, phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.


Subject(s)
Animals , Apigenin , Pharmacology , Cell Adhesion Molecules , Cell Hypoxia , Coronary Vessels , Cyclic GMP , Metabolism , Pharmacology , Cyclic GMP-Dependent Protein Kinases , Glucuronates , Pharmacology , Microfilament Proteins , NG-Nitroarginine Methyl Ester , Metabolism , Pharmacology , Phosphoproteins , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Signal Transduction , Thionucleotides , Metabolism , Pharmacology , Vasodilation , Physiology
20.
Acta Pharmaceutica Sinica ; (12): 1107-1115, 2015.
Article in Chinese | WPRIM | ID: wpr-257020

ABSTRACT

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.


Subject(s)
Blood Platelets , Blotting, Western , Calcium , Metabolism , Cyclic AMP , Metabolism , Cyclic GMP , Metabolism , Flow Cytometry , Phosphorylation , Platelet Aggregation , Reactive Oxygen Species , Metabolism , Snake Venoms , Chemistry , Thromboxane A2 , Metabolism , Thromboxane B2 , Metabolism
SELECTION OF CITATIONS
SEARCH DETAIL