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1.
Molecules ; 29(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38257283

RESUMEN

Obesity has become a major disease that endangers human health. Studies have shown that dietary interventions can reduce the prevalence of obesity and diabetes. Resistant starch (RS) exerts anti-obesity effects, alleviates metabolic syndrome, and maintains intestinal health. However, different RS types have different physical and chemical properties. Current research on RS has focused mainly on RS types 2, 3, and 4, with few studies on RS1. Therefore, this study aimed to investigate the effect of RS1 on obesity and gut microbiota structure in mice. In this study, we investigated the effect of potato RS type 1 (PRS1) on obesity and inflammation. Mouse weights, as well as their food intake, blood glucose, and lipid indexes, were assessed, and inflammatory factors were measured in the blood and tissues of the mice. We also analyzed the expression levels of related genes using PCR, with 16S rRNA sequencing used to study intestinal microbiota changes in the mice. Finally, the level of short-chain fatty acids was determined. The results indicated that PRS1 promoted host obesity and weight gain and increased blood glucose and inflammatory cytokine levels by altering the gut microbiota structure.


Asunto(s)
Microbioma Gastrointestinal , Solanum tuberosum , Humanos , Animales , Ratones , Almidón Resistente , Dieta Alta en Grasa/efectos adversos , Glucemia , ARN Ribosómico 16S , Almidón/farmacología , Obesidad/etiología
2.
BMC Plant Biol ; 22(1): 514, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36329386

RESUMEN

BACKGROUND: Grazing disturbance usually affects floral display and pollination efficiency in the desert steppe, which may cause pollen limitation in insect-pollinated plants. Effective pollination is essential for the reproductive success of insect-pollinated plants and insufficient pollen transfer may result in pollen limitation. Caragana microphylla Lam is an arid region shrub with ecological importance. Few studies have been conducted on how grazing disturbance influences pollen limitation and pollination efficiency of C. microphylla. Here, we quantify the effect of different grazing intensities on floral display, pollinator visitation frequency and seed production in the Urat desert steppe. RESULTS: In C. microphylla, supplemental hand pollination increased the seed set, and pollen limitation was the predominant limiting factor. As the heavy grazing significantly reduced the seed set in plants that underwent open-pollination, but there was no significant difference in the seed set between plants in the control plots and plants in the moderate grazing plots. Furthermore, there was a higher pollinator visitation frequency in plants in the control plots than in plants in the heavy grazing plots. CONCLUSIONS: We found that pollinator visitation frequency was significantly associated with the number of open flowers. Our findings also demonstrated that seed production is associated with pollinator visitation frequency, as indicated by increased seed production in flowers with higher pollinator visitation frequency. Therefore, this study provides insight into the effect of different grazing intensities on floral display that are important for influencing pollinator visitation frequency and pollination efficiency in desert steppes.


Asunto(s)
Flores , Herbivoria , Insectos , Polen , Polinización , Animales , Flores/fisiología , Insectos/fisiología , Plantas/parasitología , Polinización/fisiología , Clima Desértico , Herbivoria/fisiología
3.
Phytother Res ; 36(10): 3885-3899, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36017979

RESUMEN

There are currently few effective and safe pharmacologic means for inducing beige adipogenesis in humans. This study highlights the role of potato protease inhibitor II (PPI II) in regulating the browning of adipose tissue. The in vitro results showed that PPI II increased the expression of the uncoupling protein 1 (UCP1) protein and gene and beige-specific genes, including Cd137, Cited1, Tbx1, and Tmem26 in vitro. PPI II treatment for three months in diet-induced obesity mice increased the levels of the UCP1 protein in white adipose tissue, causing elevated energy expenditure, thus preventing obesity and improving glucose tolerance. Mechanistic studies further revealed that PPI II regulated the abundance and activity of ß3 adrenergic receptor (ß3 -AR) in white adipocytes. Chemical-inhibition experiments revealed the crucial role of ß3 -AR-dependent protein kinase A (PKA)-p38 kinase (p38)/extracellular signal-related kinase1/2 (ERK1/2) signaling in PPI II-mediated browning program of white adipose tissues. In summary, our findings highlight the role of PPI II in beige adipocyte differentiation and thermogenesis and provide new insights into its use in preventing obesity.


Asunto(s)
Solanum tuberosum , Tejido Adiposo Blanco , Animales , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/farmacología , Glucosa/metabolismo , Humanos , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/prevención & control , Inhibidores de Proteasas/farmacología , Transducción de Señal , Solanum tuberosum/metabolismo , Termogénesis , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
4.
Appl Microbiol Biotechnol ; 106(8): 3215-3229, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35435458

RESUMEN

It was previously believed that the microbial community in the esophagus was relatively stable, but it has been reported that different esophageal diseases have different microbial community characteristics. In this study, we recruited patients with esophageal squamous cell carcinoma (ESCC) and collected 51 pairs of tumor and adjacent non-tumor tissues for full-length 16S rDNAsequencing and qPCR to compare the differences in microbial community structure. The results of sequencing in 19 pairs of tissues showed that Proteobacteria, Firmicutes, Bacteroidetes, Deinococcus-Thermus, and Actinobacteria were the main bacteria in tumor and adjacent non-tumor tissues. At the genus level, the bacteria with the highest relative proportion in tumor and adjacent non-tumor tissues were Streptococcus and Labrys, respectively. At the same time, it was observed that the complexity of microbial interactions in tumor tissues was weaker than that of adjacent non-tumor tissues. The results also found that the relative abundance of 24 taxa was statistically different between tumor and adjacent non-tumor tissues. The findings of qPCR in 32 pairs of tissues further evidence that the relative proportions of Blautia, Treponema, Lactobacillus murinus, Peptoanaerobacter stomatis, and Fusobacteria periodonticum were statistically different in tumor and adjacent non-tumor tissues. The findings of PIRCUSt2 indicated the lipopolysaccharide biosynthesis and biotin metabolism in the microbiome of cancer tissues are more significant. This study supplements the existing information on the structure, function, and interaction of microorganisms in the esophagus in situ and provides a direction for the further exploration of the relationship between esophageal in situ microorganisms and esophageal squamous cell carcinoma. KEY POINTS: • The structure of the microbial community in esophageal cancer tissue and adjacent non-tumor tissues at the phylum level is similar • Streptococcus and Labrys are the most important bacteria in esophageal tumor tissues and adjacent non-tumor tissues, respectively • Microbial interactions in tumor tissues are stronger than in adjacent non-tumor tissues.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Microbiota , Bacterias/genética , ADN Ribosómico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Proteobacteria , Streptococcus
5.
Nutrients ; 13(11)2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34836184

RESUMEN

Armillaria luteo-virens Sacc (ALS) is a rare wild Chinese medicinal and edible basidiomycete. However, its protective effect on intestinal functions and the underlying mechanism is still unknown. This work explored the improvement of dextran sulfate sodium (DSS)-induced colitis by ALS. ALS supplementation markedly improved colitis symptoms, gut barrier integrity, and goblet loss in DSS-treated mice. In addition, ALS inhibited colonic inflammation through the inhibition/activation of the mitogen-activated protein kinases/NF-κB signaling pathway. The 16S rRNA gene-based microbiota analysis revealed that ALS altered the gut microbiota composition, decreasing the richness of Enterobacteriaceae and increasing the abundance of Lactobacillaceae. The bile-acid-targeted metabolomic analysis showed that ALS recovered the microbial bile acid metabolism in the gut, enabling the activation of the farnesoid X receptor signaling by these acids, thus maintaining the intestinal homeostasis. Importantly, broad-spectrum antibiotic treatment reduced the efficacy of ALS-induced protection from colitis. Overall, our findings suggest that ALS may represent a novel approach in the nutritional intervention to prevent colitis.


Asunto(s)
Armillaria , Ácidos y Sales Biliares/metabolismo , Colitis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Fitoterapia/métodos , Preparaciones de Plantas/farmacología , Agaricales , Animales , Colitis/metabolismo , Colon/metabolismo , Colon/patología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Inflamación/metabolismo , Masculino , Ratones , FN-kappa B/metabolismo , ARN Ribosómico 16S/metabolismo
6.
J Neurosci Nurs ; 52(5): 257-262, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32675583

RESUMEN

BACKGROUND: Constipation is frequently encountered in patients undergoing brain tumor resection. Constipation has negative effects on daily living, well-being, and individuals' quality of life. We examined the impact of acupuncture and electroacupuncture (EA) stimulation on postoperative constipation for patients undergoing brain tumor resection. METHODS: Patients undergoing brain tumor resection (n = 150) were randomly divided into a nontreatment group, an acupuncture group, and an EA group. Rome III Diagnostic Criteria, Cleveland Clinic Constipation Score, symptom assessment, Patient Assessment of Constipation Quality of Life questionnaire, Self-Rating Anxiety Scale, and a Self-Rating Depression Scale were collected. RESULTS: Acupuncture and EA were effective in relieving postoperative constipation. Electroacupuncture decreased constipation and improved quality of life scores. CONCLUSION: Acupuncture and EA are novel adjuvant therapies to treat constipation.


Asunto(s)
Neoplasias Encefálicas/cirugía , Estreñimiento/terapia , Electroacupuntura/instrumentación , Complicaciones Posoperatorias , Adulto , Anciano , China , Estreñimiento/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios
7.
Artículo en Inglés | MEDLINE | ID: mdl-32454854

RESUMEN

Glycyrrhetinic acid (GA), a hydrolysate of glycyrrhizic acid from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR-663a and its roles in TGF-ß-1-induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR-663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR-663a expression was downregulated in TGF-ß-treated HSCs. The overexpression of miR-663a inhibited HSC proliferation. TGF-ß-1was confirmed as a direct target gene of miR-663a. MiR-663a alleviated HSC activation, concomitant with decreased expression of α-smooth muscle actin (α-SMA), human α2 (I) collagen (COL1A2), TGF-ß1, TGF-ßRI, Smad4, p-Smad2, and p-Smad3. GA upregulated miR-663a expression and inhibited the TGF-ß/Smad pathway in HSCs. Further studies showed that miR-663a inhibitor treatment reversed GA-mediated downregulation of TGF-ß1, TGF-ßRI, Smad4, p-Smad2, p-Smad3, α-SMA, and CoL1A2 in TGF-ß1-treated HSCs. These results show that miR-663a suppresses HSC proliferation and activation and the TGF-ß/Smad signaling pathway, highlighting that miR-663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR-663a/TGF-ß/Smad signaling pathway.

8.
Sci Rep ; 10(1): 6574, 2020 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-32313140

RESUMEN

An appropriate tillage method must be implemented by maize growers to improve phosphorus dynamics in the soil in order to increase phosphorus uptake by plant. The objective of this study was to investigate the effects of tillage systems on phosphorus and its fractions in rhizosphere and non-rhizosphere soils under maize. An experimental field was established, with phosphate fertilizers applied to four treatment plots: continuous rotary tillage (CR), continuous no-tillage (CN), plowing-rotary tillage (PR), and plowing-no tillage (PN). Under the different tillage methods, the available P was increased in the non-rhizosphere region. However, the concentration of available P was reduced in the rhizosphere soil region. The soil available P decreased with the age of the crop until the maize reached physiological maturity. The non-rhizosphere region had 132.9%, 82.5%, 259.8%, and 148.4% more available P than the rhizosphere region under the CR, PR, CN, and PN treatments, respectively. The continuous no-tillage method (CN) improved the uptake of soil phosphate by maize. The concentrations of Ca2-P, Ca8-P, Fe-P, Al-P and O-P at the maturity stage were significantly lower than other seedling stages. However, there was no significant relationship between total P and the P fractions. Therefore, a continuous no-tillage method (CN) can be used by farmers to improve phosphorus availability for spring maize. Soil management practices minimizing soil disturbance can be used to impove phosphorus availability for maize roots, increase alkaline phosphatase activity in the rhizosphere soil and increase the abundance of different phosphorus fractions.


Asunto(s)
Fósforo/metabolismo , Raíces de Plantas/metabolismo , Rizosfera , Zea mays/metabolismo , Agricultura , China , Fertilizantes , Fosfatos/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Estaciones del Año , Microbiología del Suelo , Zea mays/crecimiento & desarrollo , Zea mays/microbiología
9.
BMC Nutr ; 4: 12, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-32153876

RESUMEN

BACKGROUND: The aims of the current study were to assess the nutritional status of 25OHD3 and retinol in a northern Chinese population using our established reliable method for the simultaneous determination of serum 25OHD3 and retinol. METHOD: We established a reliable method for the simultaneous determination of 25OHD3 and retinol using SPE and UPLC/PDA; measured the serum levels of 25OHD3 and retinol in elementary school students, middle school students, and adults (n = 1181) in northern China; and assessed their nutritional status. RESULTS: Our method had good precision, detection limit, and linear quantitative range and could process 100 samples within 12 h. The average levels of 25OHD3 and retinol were 16.1 ± 6.7 ng/ml and 328.1 ± 117.1 ng/ml, respectively, in all samples. VD deficiency was common, with a prevalence > 60% in all three age groups, and the high prevalence of VA deficiency (26.1%) was observed only in the elementary school students. CONCLUSIONS: Vitamin A supplementation should be considered for elementary school students, and vitamin D supplementation is highly recommended for all age groups in Harbin. Our method could be widely adopted in population-based studies and clinical practice.

11.
Neurology ; 87(16): 1674-1680, 2016 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-27534711

RESUMEN

OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.


Asunto(s)
Calcio de la Dieta/administración & dosificación , Demencia/dietoterapia , Suplementos Dietéticos , Anciano , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagen , Cortisona/administración & dosificación , Demencia/complicaciones , Demencia/epidemiología , Demencia/genética , Estrógenos/administración & dosificación , Femenino , Estudios de Seguimiento , Terapia de Reemplazo de Hormonas , Humanos , Estudios Longitudinales , Fracturas Osteoporóticas/complicaciones , Fracturas Osteoporóticas/dietoterapia , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/genética , Estudios Prospectivos , Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/dietoterapia , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Suecia , Insuficiencia del Tratamiento , Vitamina D/administración & dosificación
12.
World J Gastroenterol ; 21(23): 7181-90, 2015 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-26109804

RESUMEN

AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05). CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.


Asunto(s)
Dolor Crónico/terapia , Colon/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Electroacupuntura , Hiperalgesia/terapia , Hipotálamo/metabolismo , Síndrome del Colon Irritable/terapia , Médula Espinal/metabolismo , Dolor Visceral/terapia , Animales , Animales Recién Nacidos , Conducta Animal , Dolor Crónico/genética , Dolor Crónico/metabolismo , Dolor Crónico/fisiopatología , Colon/inervación , Hormona Liberadora de Corticotropina/genética , Dilatación , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hiperalgesia/genética , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Inmunohistoquímica , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/fisiopatología , Masculino , Percepción del Dolor , Umbral del Dolor , Reacción en Cadena de la Polimerasa/métodos , Presión , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Dolor Visceral/genética , Dolor Visceral/metabolismo , Dolor Visceral/fisiopatología
13.
Neural Regen Res ; 8(22): 2069-77, 2013 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-25206515

RESUMEN

Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immureactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord.

14.
Neural Regen Res ; 7(15): 1145-50, 2012 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-25722707

RESUMEN

Suspended moxibustion can decrease the expression of prokineticin 1 and its receptor in colonic tissue from rats modeling chronic visceral hyperalgesia. This study aimed to verify if rat spinal cord prokineticin 1 and its receptor contribute to the analgesic effect of suspended moxibustion in a rat model of irritable bowel syndrome where rats display chronic visceral hypersensitivity. Results showed that suspended moxibustion at Tianshu (ST25) point significantly decreased visceral sensitivity to colorectal distention in a chronic visceral hyperalgesia rat model; also protein and mRNA expression of prokineticin 1 and prokineticin receptor 1 in the spinal cord of rats was significantly decreased. Experimental findings indicate that prokineticin 1 and prokineticin receptor 1 are involved in the analgesia using suspended moxibustion in rats with chronic visceral hyperalgesia.

15.
J Chromatogr B Analyt Technol Biomed Life Sci ; 831(1-2): 288-302, 2006 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-16406846

RESUMEN

Buyang Huanwu decoction (BYHWD) is a widely used Chinese traditional compound medicine that has proved effective in treating cerebrovascular illnesses; however, its active substances have remained unknown. In this paper, serum chemistry and combined high-performance liquid chromatography (HPLC), photodiode-array detection and mass-spectrometry techniques were used to study the constituents of BYHWD from pig serum after oral administration. A total of 45 characteristic HPLC peaks were detected from serum containing drug. The chemical structures of nine of the peaks were tentatively elucidated as 7,3'-dihydroxy-4'-methoxyisoflavone-7-O-glucuronide (P1), 7-hydroxy-4'-methoxyisoflavone-7-O-glucuronide (P2), 7,2',4'-trihydroxy-3'-methoxyisoflavane-7-O-sulphate (P3), 3-hydroxy-9,10-dimethoxypterocarpan-3-O-glucuronide (P4), 7,2'-dihydroxy-3',4'-dimethoxyisoflavane-7-O-glucuronide (P5), 3-hydroxy-9,10-dimethoxypterocarpane-3-O-sulphate (P6), 4(1H)-quinolinone (P7 or P8), 4-hydroxyquinoline (P8 or P7) and oleic acid (P9). All of the identified peaks, with the exception of P9, were metabolites of the constituents of BYHWD in vivo.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Porcinos Enanos/sangre , Animales , Flavonas/análisis , Masculino , Porcinos
16.
Am J Physiol Cell Physiol ; 286(2): C222-9, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14522821

RESUMEN

The purpose of this study is to test the hypothesis that mechanical and electrical activity in adult rat ventricular myocytes (ARVM) alters responses to proapoptotic and prosurvival ligands. The effects of electrical stimulation on myocyte survival, stress signaling, response to beta-adrenergic receptor (beta-AR)-stimulated apoptosis, and neuregulin-1beta (NRG) were examined. Electrical stimulation (6.6 V/cm; 0, 2, and 5 Hz; 2-ms duration; alternating polarity) of ARVM resulted in more than 70% capture. Although ARVM paced for 48 h showed higher mitochondrial uptake of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (P < 0.05, 0 vs. 2 and 5 Hz), electrical stimulation had little effect on cell survival assessed by trypan blue uptake, CPK release, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Electrical stimulation for 24 h did not induce stress response (heat shock protein 70, 90) nor stress kinase (Erk, JNK, p38) activation. NRG stimulation of Erk and Akt was similar between paced and quiescent cells. Pacing sensitized myocytes to beta-AR-stimulated JNK phosphorylation and cell death with 0.1 microM norepinephrine (NE) in paced myocytes causing equivalent cytotoxicity to 10 microM NE in quiescent cells. NRG suppressed beta-AR-induced apoptosis through a phosphatidylinositol-3-kinase-dependent pathway in both paced and quiescent cells, although it is overwhelmed by high-NE concentration in paced cells. Thus myocyte contractility modulates both NE cytotoxicity as well as the cytoprotective effect of NRG. These results demonstrate the feasibility and importance of using electrically paced cardiomyocytes in primary culture when examining the signaling pathways of cell survival.


Asunto(s)
Apoptosis/fisiología , Contracción Miocárdica/fisiología , Miocitos Cardíacos/fisiología , Neurregulina-1/farmacología , Norepinefrina/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Estimulación Eléctrica , Técnicas Electrofisiológicas Cardíacas , Activación Enzimática/fisiología , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Ventrículos Cardíacos , Proteínas Quinasas JNK Activadas por Mitógenos , Mitocondrias Cardíacas/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Isoformas de Proteínas/farmacología , Ratas , Factores de Tiempo
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