RESUMEN
Small nucleolar RNA host genes (SNHGs) as a subset of long non-coding RNAs (lncRNAs) act critical roles in tumor progression. The present study aimed to elucidate the role and mechanisms of SNHG3 in non-small cell lung cancer (NSCLC). The correlation of SNHG3/miR-340-5p/HOXA10 with the clinicopathological features and outcomes in NSCLC was analyzed by TCGA cohort. In vitro and in vivo functional experiments were conducted to assess the role of SNHG3 in NSCLC cells. Bioinformatic analysis and luciferase gene reporter were used to estimate the interaction between miR-340-5p and SNHG3/HOXA10 3'UTR. The effects of SNHG3 and (or) miR-340-5p on HOXA10 expression were detected by qRT-PCR and Western blot analysis. As a consequence, the elevated expression of SNHG3 and HOXA10 or lowered expression of miR-340-5p was related to the lymph node infiltration, distant metastases and unfavorable prognosis in NSCLC. Ectopic expression of SNHG3 boosted the proliferation and invasion of NSCLC cells in vitro and in vivo, whereas downregulation of SNHG3 reversed these effects. Moreover, SNHG3 could bind with miR-340-5p and reduce its expression levels, and miR-340-5p attenuated SNHG3-induced tumor proliferation and HOXA10 expression in NSCLC cells. Our findings unveiled that SNHG3 might be an oncogenic factor in NSCLC by downregulating miR-340-5p.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Homeobox A10 , Humanos , Neoplasias Pulmonares/genética , MicroARNs , ARN Largo no Codificante/genéticaRESUMEN
Metabolic disorder is a major health problem and is associated with a number of metabolic diseases. Due to native hyperglycaemia and resistance to exogenous insulin, chickens as a model had used in the studies of adipose tissue biology, metabolism and obesity. But no detailed information is available about the comprehensive changes of serum metabolites at different stages of chicken embryonic development. This study employed LC/MS-QTOF to determine the changes of major functional metabolites at incubation day 14 (E14d), 19 (E19d) and hatching day 1 (H1d), and the associated pathways of differential metabolites during chicken embryonic development were analysed using Metabolite Set Enrichment Analysis method. Results showed that 39 metabolites were significantly changed from E14d to E19d and 68 metabolites were significantly altered from E19d to H1d in chicken embryos. Protein synthesis was promoted by increasing the concentrations of L-glutamine and threonine, and gonadal development was promoted through increasing oestrone content from E14d to E19d in chicken embryos, which indicated that serum glutamine, threonine and oestrone contents may be considered as the candidate indicators for assessment of early embryonic development. 2-oxoglutaric acid mainly contributed to enhancing the citric cycle, and it plays an important role in improving the growth of chicken embryos at the late development; the decreasing of L-glutamine, L-isoleucine and L-leucine contents from E19d to H1d in chicken embryonic development implied their possible functions as the feed additive during early posthatch period of broiler chickens to satisfy the growth. These results provided insights into understand the roles of serum metabolites at different developmental stages of chicken embryos, it also provides available information for chicken as a model to study metabolic disease or human obesity.
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Embrión de Pollo/metabolismo , Metabolómica , Proteómica , Tejido Adiposo , Animales , Pollos , Cromatografía Liquida , Modelos Animales de Enfermedad , Humanos , Metabolómica/métodos , Obesidad , Proteómica/métodosAsunto(s)
Aneurisma Roto , Trastornos Cerebrovasculares , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Aneurisma Roto/epidemiología , Trastornos Cerebrovasculares/epidemiología , Hong Kong/epidemiología , Humanos , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/epidemiología , PrevalenciaRESUMEN
Forty polymorphic microsatellite loci were developed from Crassostrea hongkongensis using an enriched partial genomic library with magnetic beads. The polymorphism of these loci was assessed in 30 individuals from a wild population. The allele number of the polymorphic markers ranged from 2 to 13, with an average of 5.8 per locus. The polymorphism information content ranged from 0.032 to 0.891 and 37 loci presented a medium or high level of polymorphism. The observed and expected heterozygosity values ranged from 0.033 to 1.000 and 0.033 to 0.931, respectively. Of the 40 loci, 28 were found to conform to Hardy-Weinberg equilibrium (HWE), whereas the remaining 12 showed a significant departure from HWE. The availability of these markers will aid future genetic studies in C. hongkongensis.
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Crassostrea/genética , Sitios Genéticos , Repeticiones de Microsatélite/genética , Polimorfismo Genético , AnimalesRESUMEN
The aim of the current study was to evaluate the effect of chronic dehydroepiandrosterone (DHEA) administration on steroid hormones and antioxidant parameters in aged rats. To this end, three groups of Sprague-Dawley rats were compared: young (3 months of age) untreated; aged (19 months old) untreated; and aged rats treated with 20 mg/kg DHEA for 8 weeks. Major organs of aged rats in the untreated group demonstrated physiological atrophy, compared to those of young rats; this effect appeared to have been partially reversed by DHEA treatment. Testosterone and estradiol contents were significantly decreased and aldosterone significantly increased in aged untreated, compared to young untreated rats. Steroid hormone levels were obviously reversed, however, in aged rats treated with DHEA. Additionally, superoxide dismutase activity in serum, brain, heart, and liver was decreased, and maleic dialdehyde content in heart was markedly increased in untreated aged, compared to young, rats. Importantly, these changes in brain and heart of aged rats were reversed by DHEA treatment. Heme oxygenase mRNA levels were increased and inducible nitric oxide synthase mRNA levels decreased in aged, compared to young, rats; DHEA treatment appeared to reverse these changes. These results indicate that chronic DHEA administration may have effects on steroid hormone levels and antioxidant parameters in aged rats and result in postponement of the aging process.
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Envejecimiento/sangre , Deshidroepiandrosterona/farmacología , Aldosterona/sangre , Animales , Antioxidantes/metabolismo , Peso Corporal/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Estradiol/sangre , Expresión Génica/efectos de los fármacos , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Masculino , Malondialdehído/sangre , Miocardio/enzimología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Especificidad de Órganos , Oxidación-Reducción , Ratas Sprague-Dawley , Superóxido Dismutasa/sangre , Testosterona/sangreRESUMEN
The razor clam, Sinonovacula constricta, is an important commercial bivalve and a popular mollusca food in China. Twelve polymorphic microsatellite markers were isolated from the razor clam using a partial genomic library enriched for tandem repeat sequences of (CA)16, (GA)16. Polymorphisms of these loci were evaluated in a wild population of 30 individuals. The allele number of these polymorphic markers ranged from 5-15 per locus with an average of 9.333. Observed and expected heterozygosity values ranged from 0.192-1.000 and 0.219-0.906. Polymorphism information content ranged from 0.209-0.892 with an average of 0.704. Three loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction. No significant linkage disequilibrium was detected between these loci. This set of microsatellite loci are useful for genetic studies in S. constricta.
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Bivalvos/genética , Sitios Genéticos , Repeticiones de Microsatélite/genética , Polimorfismo Genético , AnimalesRESUMEN
The Korean rockfish Sebastes schlegeli is a valuable recreational and commercial fish in China, and is cultured in land-based tanks and net cages. Fifteen microsatellite markers were developed for this species, and their polymorphisms were examined in a population. The allele number of the 15 markers ranged from 2 to 13, with an average of 5.933 per locus. The observed and expected heterozygosity values ranged from 0.063 to 0.938 (averaging 0.585), and 0.062 to 0.908 (averaging 0.642), respectively. Thirteen loci were at Hardy-Weinberg equilibrium (HWE), whereas the other two significantly deviated from the HWE after a Bonferroni's correction. No significant linkage disequilibrium was detected between the comparisons of these loci. These markers are useful for studies of population genetics, linkage mapping, and other relevant studies on S. schlegeli.
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Sitios Genéticos , Genética de Población , Repeticiones de Microsatélite , Perciformes/genética , Alelos , Animales , China , Mapeo Cromosómico , Heterocigoto , Desequilibrio de LigamientoRESUMEN
SUMMARY: This study used the "functional muscle-bone unit" concept to investigate muscle-bone interaction of the lumbar spine in subjects of varying bone mineral density. It was found that unit bone mass corresponded to a relatively more muscle mass in subjects with reduced bone mineral density, indicating a relatively higher mechanical load from muscles exerted on trabecular bone. INTRODUCTION: Bone is an architecturally adaptive tissue which responds to mechanical loading. This study is proposed to use "functional muscle-bone unit" to reflect this muscle-bone interaction at spine in subjects with different bone mineral density. METHODS: The study was carried out in young normal subjects (21 females; age, 29 ± 3) and elderly subjects (155 females; age, 73 ± 3.9) with varying bone mineral density. Cross-sectional area of paravertebral muscle groups was measured in MR images to indicate the muscle mass, while the bone mineral content by dual X-ray absorptiometry was used to represent the bone mass. The functional muscle-bone unit was calculated as the ratio between the bone mass to muscle mass. RESULTS: It showed that with aging, the muscle mass decreased with the bone mass losing. However, more pronounced reduction was found in bone mass than in muscle mass in the subjects with lower bone mineral density. CONCLUSIONS: Muscle-bone interaction was changed in elderly, especially in those with osteoporosis. Unit bone mass corresponded to a higher muscle mass in subjects with reduced bone mineral density than those normal subjects. This may be contributory to the occurrence of nontraumatic vertebral fractures in elderly subjects with reduced bone mineral density.
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Densidad Ósea/fisiología , Vértebras Lumbares/fisiopatología , Músculo Esquelético/fisiopatología , Osteoporosis Posmenopáusica/fisiopatología , Absorciometría de Fotón/métodos , Adulto , Anciano , Envejecimiento/fisiología , Femenino , Humanos , Vértebras Lumbares/patología , Músculo Esquelético/patología , Tamaño de los Órganos/fisiología , Osteoporosis Posmenopáusica/patologíaRESUMEN
UNLABELLED: The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher. INTRODUCTION: The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine. METHODS: The study cohort comprised 196 females and 163 males (age range 67-89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system. RESULTS: Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction. CONCLUSION: Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration.
Asunto(s)
Densidad Ósea/fisiología , Degeneración del Disco Intervertebral/fisiopatología , Vértebras Lumbares/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/patología , Imagen por Resonancia Magnética/métodos , Masculino , Osteoporosis/complicaciones , Osteoporosis/fisiopatología , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.
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Canales de Calcio/metabolismo , Señalización del Calcio , Calcio/metabolismo , Retículo Endoplásmico/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Actinas/metabolismo , Compuestos de Boro/farmacología , Canales de Calcio/química , Carbacol/farmacología , Línea Celular , Membrana Celular/metabolismo , Diglicéridos/metabolismo , Diglicéridos/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Ionomicina/farmacología , Compuestos Macrocíclicos , Toxinas Marinas , Oxazoles/farmacología , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/química , Estroncio/metabolismo , Canales Catiónicos TRPC , Tapsigargina/farmacología , Transfección , Fosfolipasas de Tipo C/metabolismoRESUMEN
Thyroid hormone deficiency can impair testicular function. However, knowledge of the effects of mitogen-activated protein kinase (MAPK) pathways on testicular mitochondrial oxidative damage induced by hypothyroidism is still rudimentary. This study aims to explore the possible mechanisms of testicular mitochondrial oxidative damage in hypothyroidism rats. Wistar male rats were randomly divided into control (C), low- (L), and high-hypothyroidism (H) groups (1 ml/100 g body weights (BWs)/day 0, 0.001% and 0.1% propylthiouracil, respectively) by intragastric gavage for 60 days. Blood samples were collected to measure the levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH). Testicular mitochondrial homogenates were used to measure the activities of superoxide dismutase (SOD), catalase (CAT), and Ca2+-ATPase as well as protein and mRNA expression of androgen receptor (AR), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Results showed that the BWs, testes weights, and levels of T3 and T4 were all significantly decreased and the testes coefficient and level of TSH were significantly increased in the H group. There were significant decreases in SOD activity in the H group as well as decreases in CAT and Ca2+-ATPase activities in the L and H groups. Additionally, protein expression of AR decreased significantly and protein expression of phosphorylated p38MAPK and JNK increased significantly in the H group. Therefore, the study suggests that hypothyroidism could affect male reproductive function by disturbing expression of AR, changing the activity of Ca2+-ATPase, inducing oxidative stress and then leading to activation of p38MAPK and JNK signaling in the testicular mitochondria.
Asunto(s)
Hipotiroidismo/metabolismo , Mitocondrias/metabolismo , Testículo/metabolismo , Animales , Peso Corporal , ATPasas Transportadoras de Calcio/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Tamaño de los Órganos , Estrés Oxidativo , Ratas Wistar , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transducción de Señal , Testículo/patología , Hormonas Tiroideas/sangre , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
(-)-Hydroxycitric acid (HCA), a major component of Garcinia cambogia extracts, has been shown to suppress BW gain and fat accumulation in animals and humans. However, the mechanism remains unknown. In this study, gas chromatography-mass spectrometry was used to analyse serum metabolites, and principal component analysis and partial least-squares-discriminant analysis models were generated to analyse serum metabolite changes in broiler chickens after the administration of (-)-HCA at 0, 1000, 2000 and 3000 mg/kg diets for 28 days. Metabolites showing significant changes were screened by 'variable importance in the projection' plots. The results showed that 20 metabolites in the 1000 mg/kg (-)-HCA treatment group and 16 metabolites in 3000 mg/kg (-)-HCA treatment group were significantly altered. Metabolites pathway enrichment analysis indicated that these metabolites were mainly associated with metabolism of amino acids, protein synthesis, citric acid cycle, and uric acid and fatty acid synthesis. The data indicated that (-)-HCA promoted protein synthesis by regulating the metabolic directions of amino acids. At the same time, (-)-HCA treatment inhibited fatty acid synthesis by promoting the citric acid cycle, resulting in reduced cytosolic acetyl-CoA content in broiler chickens. The present study identified global changes in metabolites and analysed the main canonical metabolic pathways in broiler chickens supplemented with (-)-HCA. These results will deepen our understanding of the mechanism of (-)-HCA's effects in animals.
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Pollos/metabolismo , Citratos/farmacología , Suplementos Dietéticos , Ácidos Grasos/biosíntesis , Metabolómica , Adipogénesis , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Citratos/química , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Garcinia cambogia/química , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología , Biosíntesis de ProteínasRESUMEN
Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Deshidroepiandrosterona/farmacología , Hepatocitos/efectos de los fármacos , Gotas Lipídicas/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Animales , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Embrión de Pollo , Evaluación Preclínica de Medicamentos , Metabolismo de los Lípidos/efectos de los fármacos , Cultivo Primario de CélulasRESUMEN
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
Asunto(s)
Adenocarcinoma/patología , Antígeno B7-H1/análisis , Proliferación Celular , Neoplasias Pulmonares/patología , Linfocitos T/patología , Células A549 , Animales , Anticuerpos Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Células Cultivadas , Citometría de Flujo , Humanos , Inmunoterapia/métodos , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales , Neoplasias del Bazo/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The growth behavior of intermetallic compounds (IMCs) at the liquid-solid interfaces in Cu/Sn/Cu interconnects during reflow at 250 °C and 280 °C on a hot plate was investigated. Being different from the symmetrical growth during isothermal aging, the interfacial IMCs showed clearly asymmetrical growth during reflow, i.e., the growth of Cu6Sn5 IMC at the cold end was significantly enhanced while that of Cu3Sn IMC was hindered especially at the hot end. It was found that the temperature gradient had caused the mass migration of Cu atoms from the hot end toward the cold end, resulting in sufficient Cu atomic flux for interfacial reaction at the cold end while inadequate Cu atomic flux at the hot end. The growth mechanism was considered as reaction/thermomigration-controlled at the cold end and grain boundary diffusion/thermomigration-controlled at the hot end. A growth model was established to explain the growth kinetics of the Cu6Sn5 IMC at both cold and hot ends. The molar heat of transport of Cu atoms in molten Sn was calculated as + 11.12 kJ/mol at 250 °C and + 14.65 kJ/mol at 280 °C. The corresponding driving force of thermomigration in molten Sn was estimated as 4.82 × 10(-19) N and 6.80 × 10(-19) N.
RESUMEN
The effect of testosterone on the activity of ornithine decarboxylase (ODC), its protein level and immunocytochemical distribution were examined in the mouse kidney. Male BALB C mice at 8 weeks of age were used throughout. Fourteen hours before death, they received a subcutaneous injection of testosterone (1 mg/animal) or solvent to measure renal ODC activity or to detect the distribution of ODC immunoreactivity in the kidney. Renal ODC activity and the content of the enzyme were markedly increased after testosterone treatment. Histologically, few cells that were obviously immunoreactive to ODC were observed in the control animals and in the testosterone-treated animals a marked increase in ODC immunoreactivity was observed only in the cortex. ODC immunoreactive cells were located diffusely in the proximal tubule. In the pars recta, cells were stained weakly and homogeneously, while in the pars convoluta, the luminal surface of the cells showed stronger immunoreactivity. Moreover, many granule-like particles that were strongly ODC immunoreactive were observed inside the lumen of the pars convoluta. These results show that testosterone treatment induces an increase in ODC content in certain cells located in the proximal tubule of the cortex.
Asunto(s)
Túbulos Renales Proximales/enzimología , Ornitina Descarboxilasa/metabolismo , Testosterona/metabolismo , Animales , Inmunohistoquímica , Túbulos Renales Proximales/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Testosterona/farmacologíaRESUMEN
Polyamines such as putrescine, spermidine and spermine have been thought to play an important role in thyroid growth induced by goitrogens. Reduced biosynthesis of these polyamines might play a role in the antigoitrogenic effects of excess iodide. This study was designed to examine the effect of potassium iodide (KI) on ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of polyamines. Thyroidal ODC activity, protein content and mRNA were increased in rats made hypothyroid by 10 days of propylthiouracil treatment. The increase in ODC activity was suppressed after subcutaneous injection of KI (13mg/kg body weight); the apparent half-life of ODC activity after the treatment was estimated to be 19 min and the maximum suppression (90%) was seen 60 min after the treatment. On the other hand, administration of iodine-containing compounds including L-thyroxine, L-di-iodotyrosine,amiodarone, iopanoic acid and erythrosine showed no significant effect on ODC activity. The inhibitory effect of excess iodide was not reversed by pretreatment with dibutyryl cAMP and theophylline. The amount of immunoreactive ODC protein was reduced by iodide treatment (40%). However, the decrease was not as great as the decrease in ODC activity (90%). No significant change in thyroidal ODC mRNA content was seen 1 and 3 h following KI treatment. These results suggest that excess iodide reduces ODC activity in the rat thyroid gland by a post-transcriptional mechanism.
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Hipotiroidismo/enzimología , Inhibidores de la Ornitina Descarboxilasa , Yoduro de Potasio/farmacología , Glándula Tiroides/enzimología , Animales , Northern Blotting , Bucladesina/farmacología , Depresión Química , Masculino , Ornitina Descarboxilasa/genética , Ornitina Descarboxilasa/metabolismo , Propiltiouracilo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Teofilina/farmacología , Glándula Tiroides/efectos de los fármacosRESUMEN
Pancreastatin (PST) is known to inhibit glucose-stimulated insulin release both in vivo and in vitro, but it has not been determined whether PST acts directly on pancreatic B-cells and no study has been reported on the effect of PST on the intracellular free Ca2+ concentration ([Ca2+]i) in pancreatic islet cells. In the present study, by using the dissociated rat pancreatic B-cells, we examined the effects of PST on the increase in [Ca2+]i induced by several insulin secretagogues, and compared them with those of somatostatin (SRIF). PST (1-100 nM) dose-dependently inhibited the glucose-induced rise in [Ca2+]i in single pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-induced rise in [Ca2+]i. These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 microM) with 5.5 mM glucose induced a biphasic increase in [Ca2+]i in single islet cells. SRIF (10 nM) suppressed the second phase in [Ca2+]i increase without affecting the first phase. In contrast, PST (100 nM) had no effect on the ACh-induced response. Gastric inhibitory polypeptide (100 nM) with 5.5 mM glucose induced a rise in [Ca2+]i in single islet cells. SRIF inhibited this increase, but PST did not. Both PST and SRIF failed to affect the sustained rise in [Ca2+]i evoked by excess K+. These results suggest that PST and SRIF suppress the glucose-induced insulin secretion at least partly by inhibiting the rise in [Ca2+]i in pancreatic B-cells. Furthermore, PST may suppress the glucose-induced rise in [Ca2+]i via a mechanism different from that of SRIF.
Asunto(s)
Calcio/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Hormonas Pancreáticas/farmacología , Somatostatina/farmacología , Acetilcolina/farmacología , Animales , Células Cultivadas , Colecistoquinina/farmacología , Cromogranina A , Polipéptido Inhibidor Gástrico/farmacología , Glucosa/farmacología , Antagonistas de Hormonas/farmacología , Masculino , Potasio/farmacología , Ratas , Ratas WistarRESUMEN
An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent candidate for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell. Endocrinol., 96 (1993) 85-90) that GLP-1 increased both insulin secretion and the efflux of 45Ca2+ in a Na(+)-dependent manner. Further, GLP-1 depolarizes the pancreatic beta cells in the presence of high concentration of glucose. Here, we report the effect of GLP-1 on the membrane potential with a physiological concentration of glucose in perforated patch clamp of primary cultured rat beta cells. 10 nM GLP-1 depolarized the beta cell, which was completely reversed by replacing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+ channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpolarizing the cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by a prior replacement of Na+ with NMDG. In addition, GLP-1 slightly augmented the long-lasting Ba2+ current, which was reverted to the control level by a selective inhibitor of protein kinase A, H-89. These results indicate: (i) GLP-1 depolarizes the beta cell by activating the membrane Na+ permeability; (ii) GLP-1 slightly modulates the L-type Ca2+ channel probably through protein kinase A; and (iii) at least in part, these mechanisms may be involved in the insulin secretion induced by GLP-1.
Asunto(s)
Islotes Pancreáticos/efectos de los fármacos , Hormonas Pancreáticas/farmacología , Péptidos/farmacología , Sodio/metabolismo , Sulfonamidas , Animales , Bario/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Glucagón/inmunología , Péptido 1 Similar al Glucagón , Glucosa/metabolismo , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Isoquinolinas/farmacología , Masculino , Meglumina/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Técnicas de Placa-Clamp , Precursores de Proteínas/farmacología , Ratas , Ratas WistarRESUMEN
Asymmetrical appearances of normal anatomical structures can sometimes mimic pathology. We present a case where asymmetry of the gyri recti was interpreted as a suprasellar mass on axial CT scanning. The true nature of the apparent abnormality was revealed by coronal magnetic resonance imaging (MRI). We also present six further cases where asymmetrical gyri recti were noted as incidental findings on coronal MRI scans. This is a common, but important, normal anatomical variant, which should not be mistaken for pathology.