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1.
Sci Rep ; 11(1): 23227, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34853400

RESUMEN

Roses are widely used as cut flowers worldwide. Petal senescence confines the decorative quality of cut rose flowers, an impressively considerable economic loss. Herein, we investigated the SUMO1/SUMO E3 ligase SIZ1 signaling pathway during bud opening, and petal senescence of cut rose flowers. Our results exhibited that the higher expression of SUMO1 and SUMO E3 ligase SIZ1 during bud opening was accompanied by lower endogenous H2O2 accumulation arising from higher expression and activities of SOD, CAT, APX, and GR, promoting proline accumulation by increasing P5CS expression and activity and enhancing GABA accumulation by increasing GAD expression and activity. In harvested flowers, lower expressions of SUMO1 and SUMO E3 ligase SIZ1 during petal senescence were associated with higher endogenous H2O2 accumulation due to lower expression and activities of SOD, CAT, APX, and GR. Therefore, promoting the activity of the GABA shunt pathway as realized by higher expression and activities of GABA-T and SSADH accompanied by increasing OAT expression and activity for sufficiently supply proline in rose flowers during petal senescence might serve as an endogenous antisenescence mechanism for slowing down petals senescence by avoiding endogenous H2O2 accumulation. Following phytosulfokine α (PSKα) application, postponing petal senescence in cut rose flowers could be ascribed to higher expression of SUMO1 and SUMO E3 ligase SIZ1 accompanied by higher expression and activities of SOD, CAT, APX, and GR, higher activity of GABA shunt pathway as realized by higher expression and activities of GAD, GABA-T, and SSADH, higher expression and activities of P5CS and OAT for supplying proline and higher expression of HSP70 and HSP90. Therefore, our results highlight the potential of the PSKα as a promising antisenescence signaling peptide in the floriculture industry for postponing senescence and extending the vase life of cut rose flowers.


Asunto(s)
Flores/efectos de los fármacos , Hormonas Peptídicas/farmacología , Proteínas de Plantas/farmacología , Rosa/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas , Peróxido de Hidrógeno/metabolismo , Proteína SUMO-1/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo
2.
Peptides ; 120: 170116, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31348991

RESUMEN

Insulin-like peptide 5 (INSL5) is a member of the insulin-like family of peptides. It has been reported to be orexigenic in rodent models of obesity with impaired glucose metabolism. We attempted to confirm this property as a first step in establishing the ability of INSL5 to successfully integrate with other agents more proven in their ability to reverse obesity and improve metabolism. INSL5 was chemically synthesized by two alternative methods to a native form and one that was site-specifically conjugated to a 20 KDa polyethylene glycol (PEG) polymer. The pharmacology of each peptide was assessed by high-dose chronic administration in normal and obese mice. INSL5 failed to produce pharmacologically relevant effects on food intake, body weight or glucose control indicative of a negligible role of the peptide in the control of feeding and glucose metabolism.


Asunto(s)
Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Glucosa/metabolismo , Obesidad/metabolismo , Hormonas Peptídicas/farmacología , Animales , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/patología , Hormonas Peptídicas/síntesis química , Hormonas Peptídicas/química
3.
Brain Res ; 1715: 188-195, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30930149

RESUMEN

Phoenixin is a novel neuropeptide initially associated with reproductive functions, but subsequently also with feeding behavior. Nesfatin-1 is also involved in the regulation of food intake and has been shown to largely colocalize with phoenixin in the rat brain; however, a functional link is missing so far. The current study investigated whether phoenixin activates nesfatin-1 immunoreactive nuclei in the rat brain. Male Sprague Dawley rats chronically equipped with an intracerebroventricular cannula were injected with vehicle (5 µl ddH2O) or phoenixin (1.7 nmol in 5 µl ddH2O, n = 5-6 group). Behavior was assessed manually and c-Fos as well as nesfatin-1 immunoreactivity using immunohistochemistry. Phoenixin significantly increased feeding and drinking behavior as well as locomotor activity compared to vehicle (p < 0.01). Moreover, phoenixin injected intracerebroventricularly (icv) activated several nuclei throughout the rat brain as assessed using c-Fos; the number of c-Fos/nesfatin-1 immunoreactive neurons was increased in the lateral septal nucleus (4-fold), supraoptic nucleus (107-fold), paraventricular nucleus (6-fold) and the nucleus of the solitary tract (18-fold) compared to vehicle (p < 0.05). In summary, phoenixin activates several nesfatin-1 immunoreactive nuclei in the rat brain. This activation may play a role in the modulation of food intake.


Asunto(s)
Conducta Alimentaria/efectos de los fármacos , Nucleobindinas/metabolismo , Hormonas Peptídicas/farmacología , Animales , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al ADN/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Hipotálamo/metabolismo , Infusiones Intraventriculares , Masculino , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Hormonas Peptídicas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-30114526

RESUMEN

Phoenixin (Pnx) is an endogenous peptide known to be involved in reproduction and food intake in rats, with two active isoforms, phoenixin-14 (Pnx-14) and phoenixin-20 (Pnx-20). However, little is known about the functions of Pnx in teleost. Here, pnx was cloned and was detected in all tissues of both male and female in spotted scat (Scatophagus argus), including growth axis, hypothalamus, pituitary, and liver. Real-time PCR analysis showed that pnx in the hypothalamus increased significantly after 2 d and 7 d fasting, while reduced significantly after re-feeding (P < 0.05). When pituitary and liver fragments were cultured in vitro with Pnx-14 and Pnx-20 (10 nM and 100 nM) for 6 h, the expression of ghrhr (growth hormone-releasing hormone receptor) and gh (growth hormone) in the pituitary, and ghr1 (growth hormone receptor 1) in the liver increased significantly, except ghr2 (growth hormone receptor 2) incubated with 10 nM and 100 nM Pnx-20 and ghr1 incubated with 10 nM Pnx-20. Similarly, the expression of ghrhr and gh in the pituitary, as well as ghr1 and ghr2 in the liver, increased significantly after injecting S. argus with Pnx-14 and Pnx-20 (10 ng/g and 100 ng/g body weight). These results indicate that Pnx is likely to be involved in the regulation of food intake, and also regulates the growth of S. argus by increasing ghrhr and gh expression in the pituitary, ghr1 and ghr2 in the liver, and ghr1 directly in the liver.


Asunto(s)
Ingestión de Energía , Proteínas de Peces/metabolismo , Regulación del Desarrollo de la Expresión Génica , Hormonas Hipotalámicas/metabolismo , Hipotálamo/metabolismo , Hormonas Peptídicas/metabolismo , Perciformes/fisiología , Animales , Acuicultura , China , Ingestión de Energía/efectos de los fármacos , Femenino , Proteínas de Peces/administración & dosificación , Proteínas de Peces/genética , Proteínas de Peces/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hormona del Crecimiento/agonistas , Hormona del Crecimiento/genética , Hormona del Crecimiento/metabolismo , Hormonas Hipotalámicas/administración & dosificación , Hormonas Hipotalámicas/genética , Hormonas Hipotalámicas/farmacología , Hipotálamo/efectos de los fármacos , Inyecciones Intraperitoneales , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Especificidad de Órganos , Hormonas Peptídicas/administración & dosificación , Hormonas Peptídicas/genética , Hormonas Peptídicas/farmacología , Perciformes/crecimiento & desarrollo , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Isoformas de Proteínas/administración & dosificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , Distribución Aleatoria , Receptores de Neuropéptido/agonistas , Receptores de Neuropéptido/genética , Receptores de Neuropéptido/metabolismo , Receptores de Hormona Reguladora de Hormona Hipofisaria/agonistas , Receptores de Hormona Reguladora de Hormona Hipofisaria/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/metabolismo , Receptores de Somatotropina/agonistas , Receptores de Somatotropina/genética , Receptores de Somatotropina/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Técnicas de Cultivo de Tejidos/veterinaria , Aumento de Peso
5.
Lipids ; 53(4): 429-436, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29655176

RESUMEN

Growth hormone (GH) release is a process that is well regulated by several factors, including GH secretagogues. GH can mediate the regulation of the fatty acid level and composition. The aim of this study was to determine the effect of a synthetic GH secretagogue peptide (A233) on the growth and fatty acid composition in tilapia (Oreochromis niloticus). To address this objective, we administrated a diet supplemented with A233 to juvenile tilapia for 60 days. The group fed with a diet supplemented with 600 µg of A233 per kg of feed increased in weight (4.81 ± 0.09 g) and specific growth rate (2.49 ± 0.03%/day) compared to the control diet group (3.63 ± 0.08 g, 2.07 ± 0.04%/day; respectively) (p < 0.001). In the muscle, the total lipids for the control diet group were higher than that in the group fed with 600 µg of A233 per kg feed; however, no differences were detected in the liver. In both tissues, the patterns of fatty acid composition and content were generally similar, with some exceptions. Tilapia fed with 600 µg of A233 per kg of feed showed, in liver and muscle, a significantly higher composition and content of n-3 polyunsaturated fatty acids (such as 20:5n-3, 22:5n-3, 22:6n-3) and n-3/n-6 PUFA than animals fed with the control diet. To our knowledge, this is the first report on the the effects of natural or synthetic GH secretagogues (GHS) on fatty acid composition, implying an increase in the nutritional quality of the tilapia.


Asunto(s)
Cíclidos/crecimiento & desarrollo , Cíclidos/metabolismo , Ácidos Grasos Omega-3/metabolismo , Hígado/efectos de los fármacos , Músculos/efectos de los fármacos , Hormonas Peptídicas/farmacología , Secretagogos/farmacología , Animales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Hígado/metabolismo , Músculos/metabolismo , Hormonas Peptídicas/administración & dosificación , Hormonas Peptídicas/química , Secretagogos/administración & dosificación , Secretagogos/química
6.
Genes Brain Behav ; 16(4): 439-448, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27862969

RESUMEN

Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats.


Asunto(s)
Apetito/efectos de los fármacos , Ghrelina/metabolismo , Hipotálamo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenilpropanolamina/farmacología , Animales , Anorexia/inducido químicamente , Apetito/fisiología , Peso Corporal , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Hipotálamo/metabolismo , Masculino , Neuropéptido Y/metabolismo , Estrés Oxidativo/fisiología , Hormonas Peptídicas/farmacología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Receptores de Ghrelina/antagonistas & inhibidores , Receptores de Ghrelina/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-26151373

RESUMEN

Both intrinsic and extrinsic factors modulate food intake and glycemia in vertebrates, in part through interactions with hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons. The objective of this project was to elucidate the effects of ghrelin (GHRL), gastrin-releasing peptide (GRP), cholecystokinin (CCK), glucagon-like peptide (GLP), pancreatic polypeptide (PP), and peptide YY (PYY) on appetite, glycemia, and hypothalamic expression of NPY and POMC in channel catfish. Catfish were injected intraperitoneally with a single peptide at concentrations of either 0 (control), 50, 100, or 200 ng/g body weight (BW), respectively. Fish were allowed to recover for 30 min, and then fed to satiation over 1 h. Feed intake was determined 1h post-feeding. Catfish injected with GHRL at 50 and 100 ng/g BW and GRP at 200 ng/g BW consumed significantly (P<0.05) less feed compared to controls. A tendency (P<0.1) to suppress feed intake was also observed in the 200 ng/g BW GHRL and PP treatments. PYY, CCK, and GLP had no effects on feed intake. Glycemia was not affected by GHRL, GRP, PP, and PYY treatments, but was suppressed by CCK. A tendency toward lower plasma glucose concentrations was observed in fish administered GLP at 50 ng/g BW. Hypothalamic NPY expression was highly variable and not significantly affected by treatment. POMC expression was also variable, but tended to be reduced by the highest concentration of CCK. These results provide new insight into the roles and regulation of gut neuropeptides in catfish appetite and glycemia.


Asunto(s)
Glucemia/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Ictaluridae/fisiología , Neuropéptido Y/genética , Hormonas Peptídicas/farmacología , Proopiomelanocortina/genética , Animales , Colecistoquinina/administración & dosificación , Colecistoquinina/farmacología , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/fisiología , Péptido Liberador de Gastrina/administración & dosificación , Péptido Liberador de Gastrina/farmacología , Expresión Génica/efectos de los fármacos , Ghrelina/administración & dosificación , Ghrelina/farmacología , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Hipotálamo/metabolismo , Ictaluridae/sangre , Ictaluridae/genética , Inyecciones Intraperitoneales , Polipéptido Pancreático/administración & dosificación , Polipéptido Pancreático/farmacología , Hormonas Peptídicas/administración & dosificación , Péptido YY/administración & dosificación , Péptido YY/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
Bull Exp Biol Med ; 159(1): 38-40, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26033586

RESUMEN

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.


Asunto(s)
Antioxidantes/análisis , Depresores del Apetito/farmacología , Sobrepeso/tratamiento farmacológico , Fragmentos de Péptidos/farmacología , Hormonas Peptídicas/farmacología , Secuencia de Aminoácidos , Animales , Depresores del Apetito/administración & dosificación , Depresores del Apetito/uso terapéutico , Catalasa/sangre , Dieta Alta en Grasa/efectos adversos , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Masculino , Datos de Secuencia Molecular , Sobrepeso/sangre , Sobrepeso/etiología , Fragmentos de Péptidos/administración & dosificación , Hormonas Peptídicas/administración & dosificación , Hormonas Peptídicas/uso terapéutico , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre
9.
Peptides ; 48: 137-46, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23965296

RESUMEN

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Mucosa Gástrica/metabolismo , Ghrelina/farmacología , Gastropatías/tratamiento farmacológico , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Ghrelina/metabolismo , Hipotálamo/efectos de los fármacos , Neuronas/efectos de los fármacos , Hormonas Peptídicas/farmacología , Ratas , Receptores de Ghrelina/metabolismo , Estómago/efectos de los fármacos , Estómago/fisiología , Gastropatías/metabolismo , Gastropatías/fisiopatología , Estreptozocina/metabolismo
10.
Regul Pept ; 186: 77-82, 2013 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-23891980

RESUMEN

Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5µg/2µl) was administrated once a day in all experiments. Furthermore, 0.2mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.


Asunto(s)
Analgésicos Opioides/farmacología , Morfina/farmacología , Antagonistas de Narcóticos/farmacología , Hormonas Peptídicas/farmacología , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Animales , Ansiedad/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Tolerancia a Medicamentos , Masculino , Ratones , Naloxona/farmacología , Nocicepción/efectos de los fármacos
11.
Biochem Biophys Res Commun ; 436(2): 278-82, 2013 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-23743192

RESUMEN

Plants have been used for the treatment of diabetes since time immemorial. In the present study, insulin-like protein (ILP) is purified from Costus igneus belonging to family Costaceae from Western ghats of India. The ILP showed cross reactivity with murine anti-insulin antibodies hence was purified by affinity chromatography using anti-insulin antibodies. The characterization of ILP showed that it is structurally different from insulin but functionally similar. The ILP showed a hypoglycemic activity in an in vitro assay with insulin responsive cell line RIN 5f. Interestingly ILP showed significant decrease in blood glucose level when administered orally in oral glucose tolerance test. This was compared to insulin a positive control given intraperitoneally in streptozotocine induced diabetic mice. There was no toxic effect seen on animals after administrating the ILP. Therefore we conclude that the ILP purified in the present study from C. igneus is a novel protein having hypoglycemic activity.


Asunto(s)
Costus/metabolismo , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Proteínas de Plantas/farmacología , Administración Oral , Animales , Glucemia/metabolismo , Western Blotting , Línea Celular Tumoral , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/prevención & control , Glucosa/metabolismo , Glucosa/farmacocinética , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Inyecciones Intraperitoneales , Insulina/administración & dosificación , Insulina/farmacología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Masculino , Ratones , Hormonas Peptídicas/administración & dosificación , Hormonas Peptídicas/aislamiento & purificación , Hormonas Peptídicas/farmacología , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Reguladores del Crecimiento de las Plantas/aislamiento & purificación , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/metabolismo , Proteínas de Plantas/administración & dosificación , Proteínas de Plantas/aislamiento & purificación , Factores de Tiempo
12.
Int J Radiat Oncol Biol Phys ; 83(3): e409-15, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22420966

RESUMEN

PURPOSE: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. METHODS AND MATERIALS: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. RESULTS: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-α-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-α, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. CONCLUSIONS: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.


Asunto(s)
Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Hormonas Peptídicas/farmacología , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Estomatitis/tratamiento farmacológico , Animales , Línea Celular , Cricetinae , Citoprotección/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/efectos de la radiación , Células Epiteliales/citología , Células Epiteliales/efectos de la radiación , Humanos , Mesocricetus , Estomatitis/etiología , Factor de Necrosis Tumoral alfa
13.
Neuroscience ; 166(2): 455-63, 2010 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-20056135

RESUMEN

Neuronostatin (NST) is a newly identified peptide of 13-amino acids encoded by the somatostatin (SST) gene. Using a rabbit polyclonal antiserum against the human NST, neuronostatin-immunoreactive (irNST) cells comparable in number and intensity to somatostatin immunoreactive (irSST) cells were detected in the hypothalamic periventricular nucleus. Fewer and/or less intensely labeled irNST cells were noted in other regions such as the hippocampus, cortex, amygdala, and cerebellum. Double-labeling hypothalamic sections with NST- and SST-antiserum revealed an extensive overlapping of irNST and irSST cells in the periventricular nucleus. Pre-absorption of the NST-antiserum with NST (1 microg/ml) but not with SST (1 microg/ml) abrogated irNST and vice versa. The activity of NST on dissociated and cultured hypothalamic neurons was assessed by the Ca(2+) imaging method. NST (10, 100, 1000 nM) concentration-dependently elevated intracellular Ca(2+) concentrations [Ca(2+)](i) in a population of hypothalamic neurons with two distinct profiles: (1) a fast and transitory increase in [Ca(2+)](i), and (2) an oscillatory response. Whereas, SST (100 nM) reduced the basal [Ca(2+)](i) in 21 of 61 hypothalamic neurons examined; an increase was not observed in any of the cells. Optical imaging with a slow-responding voltage sensitive dye DiBAC(4)(3) showed that NST (100 nM) depolarized or hyperpolarized; whereas, SST (100 nM) hyperpolarized a population of hypothalamic neurons. The result shows that NST and SST, though derived from the same precursor protein, exert different calcium mobilizing effects on cultured rat hypothalamic neurons, resulting in diverse cellular activities.


Asunto(s)
Calcio/metabolismo , Hipotálamo/metabolismo , Neuronas/metabolismo , Hormonas Peptídicas/metabolismo , Somatostatina/metabolismo , Análisis de Varianza , Animales , Células Cultivadas , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Inmunohistoquímica , Masculino , Potenciales de la Membrana/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Hormonas Peptídicas/farmacología , Ratas , Ratas Sprague-Dawley , Somatostatina/farmacología
14.
J Exp Biol ; 212(Pt 24): 3961-76, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19946074

RESUMEN

pQDLDHVFLRFamide is a highly conserved crustacean neuropeptide with a structure that places it within the myosuppressin subfamily of the FMRFamide-like peptides. Despite its apparent ubiquitous conservation in decapod crustaceans, the paracrine and/or endocrine roles played by pQDLDHVFLRFamide remain largely unknown. We have examined the actions of this peptide on the cardiac neuromuscular system of the American lobster Homarus americanus using four preparations: the intact animal, the heart in vitro, the isolated cardiac ganglion (CG), and a stimulated heart muscle preparation. In the intact animal, injection of myosuppressin caused a decrease in heartbeat frequency. Perfusion of the in vitro heart with pQDLDHVFLRFamide elicited a decrease in the frequency and an increase in the amplitude of heart contractions. In the isolated CG, myosuppressin induced a hyperpolarization of the resting membrane potential of cardiac motor neurons and a decrease in the cycle frequency of their bursting. In the stimulated heart muscle preparation, pQDLDHVFLRFamide increased the amplitude of the induced contractions, suggesting that myosuppressin modulates not only the CG, but also peripheral sites. For at least the in vitro heart and the isolated CG, the effects of myosuppressin were dose-dependent (10(-9) to 10(-6) mol l(-1) tested), with threshold concentrations (10(-8)-10(-7) mol l(-1)) consistent with the peptide serving as a circulating hormone. Although cycle frequency, a parameter directly determined by the CG, consistently decreased when pQDLDHVFLRFamide was applied to all preparation types, the magnitudes of this decrease differed, suggesting the possibility that, because myosuppressin modulates the CG and the periphery, it also alters peripheral feedback to the CG.


Asunto(s)
Crustáceos/química , Corazón/efectos de los fármacos , Nephropidae/efectos de los fármacos , Nephropidae/fisiología , Sistema Nervioso/efectos de los fármacos , Neuropéptidos/farmacología , Hormonas Peptídicas/farmacología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , FMRFamida/farmacología , Ganglios de Invertebrados/efectos de los fármacos , Ganglios de Invertebrados/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Datos de Secuencia Molecular , Contracción Miocárdica/efectos de los fármacos , Miocardio , Neuropéptidos/química , Neuropéptidos/genética , Hormonas Peptídicas/química , Perfusión , Reproducibilidad de los Resultados , Factores de Tiempo
15.
Yao Xue Xue Bao ; 43(6): 553-8, 2008 Jun.
Artículo en Chino | MEDLINE | ID: mdl-18822954

RESUMEN

Heme oxygenase-1 (HO-1) is a cellular stress protein, and its expression plays an important regulatory role in a lot of physiological and pathological processes. Although the expression of HO-1 in most tissues of body is low, a number of clinical and pharmacological experiments have proved that many compounds can induce HO-1 expression. The increase of HO-1 expression is the result of regulating different signaling pathways and transcription factors, and this induction of HO-1 is suggested to be partially therapeutic efficacy of these compounds. This article summarizes some kinds of compounds in this field of research at home and abroad over the last 10 years, and provides a brief analysis of the mechanism.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hemo-Oxigenasa 1/metabolismo , Óxido Nítrico/farmacología , Hormonas Peptídicas/farmacología , Transducción de Señal , Animales , Antineoplásicos/farmacología , Antioxidantes/farmacología , Cumarinas/farmacología , Inducción Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica , Hemo-Oxigenasa 1/genética , Humanos , Lovastatina/farmacología , Probucol/farmacología , Factores de Transcripción/metabolismo
16.
Endocrinology ; 148(6): 3004-12, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17347304

RESUMEN

Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.


Asunto(s)
Composición Corporal/efectos de los fármacos , Caquexia/etiología , Caquexia/patología , Ingestión de Alimentos/efectos de los fármacos , Neoplasias/complicaciones , Hormonas Peptídicas/farmacología , Animales , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ghrelina , Hormona del Crecimiento/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Neoplasias/patología , Ratas , Ratas Endogámicas F344 , Carga Tumoral/efectos de los fármacos
17.
Regul Pept ; 140(1-2): 94-100, 2007 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-17187875

RESUMEN

This study aimed to clarify the interaction of tumor necrosis factor-alpha (TNF-alpha), an anorexigenic cytokine, with ghrelin, an orexigenic peptide secreted by the stomach lining, and hypothalamic neuropeptides in the regulation of food intake in mice. The peripheral administration of TNF-alpha dose-dependently decreased the 24-h cumulative food intake compared with the administration of saline. Reduced food intake was observed at 6 h and 24 h. The same TNF-alpha treatment significantly decreased the plasma level of ghrelin at 6 h and 24 h after treatment compared with the control levels. These changes were accompanied by a significant reduction in the expression of ghrelin mRNA in the stomach at 24 h after treatment. TNF-alpha treatment also resulted in a significant increase in expression of pro-opiomelanocortin (POMC) mRNA and a significant decrease in expression of agouti-related protein (AGRP) mRNA in the hypothalamus at 6 h after treatment. Finally, the pre-administration of ghrelin, reversed the TNF-alpha-induced hypophagia in mice at 6 and 24 h. Taken together, these findings suggest that hypothalamic POMC and AGRP and stomach ghrelin may be involved in TNF-alpha-induced hypophagia in mice.


Asunto(s)
Hiperfagia/genética , Neuropéptidos/genética , Hormonas Peptídicas/genética , Factor de Necrosis Tumoral alfa/farmacología , Animales , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Mucosa Gástrica/metabolismo , Expresión Génica/efectos de los fármacos , Ghrelina , Humanos , Hiperfagia/inducido químicamente , Hiperfagia/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ratones , Ratones Endogámicos C57BL , Hormonas Peptídicas/sangre , Hormonas Peptídicas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estómago/efectos de los fármacos , Factores de Tiempo
18.
Endocrinology ; 148(1): 148-59, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17053024

RESUMEN

Ghrelin is an endogenous ligand for the GH secretagogue receptor, produced and secreted mainly from the stomach. Ghrelin stimulates GH release and induces positive energy balances. Previous studies have reported that ghrelin inhibits apoptosis in several cell types, but its antiapoptotic effect in neuronal cells is unknown. Therefore, we investigated the role of ghrelin in ischemic neuronal injury using primary hypothalamic neurons exposed to oxygen-glucose deprivation (OGD). Here we report that treatment of hypothalamic neurons with ghrelin inhibited OGD-induced cell death and apoptosis. Exposure of neurons to ghrelin caused rapid activation of ERK1/2. Ghrelin-induced activation of ERK1/2 and the antiapoptotic effect of ghrelin were blocked by chemical inhibition of MAPK, phosphatidylinositol 3 kinase, protein kinase C, and protein kinase A. Ghrelin attenuated OGD-induced activation of c-Jun NH2-terminal kinase and p-38 but not ERK1/2. We also investigated ghrelin regulation of apoptosis at the mitochondrial level. Ghrelin protected cells from OGD insult by inhibiting reactive oxygen species generation and stabilizing mitochondrial transmembrane potential. In addition, ghrelin-treated cells showed an increased Bcl-2/Bax ratio, prevention of cytochrome c release, and inhibition of caspase-3 activation. Finally, in vivo administration of ghrelin significantly reduced infarct volume in an animal model of ischemia. Our data indicate that ghrelin may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways.


Asunto(s)
Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Hipotálamo/patología , Neuronas/efectos de los fármacos , Hormonas Peptídicas/farmacología , Animales , Apoptosis/fisiología , Isquemia Encefálica/patología , Caspasa 3/metabolismo , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Citocromos c/metabolismo , Modelos Animales de Enfermedad , Ghrelina , Glucosa/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neuronas/patología , Oxígeno/farmacología , Hormonas Peptídicas/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína Quinasa C/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Ghrelina , Proteína X Asociada a bcl-2/metabolismo
19.
Endocrinology ; 148(1): 21-6, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17008393

RESUMEN

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Hormona del Crecimiento/metabolismo , Hipotálamo/efectos de los fármacos , Hormonas Peptídicas/farmacología , Animales , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Metabolismo Energético/fisiología , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Ghrelina , Hipotálamo/metabolismo , Hipotálamo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Hormonas Peptídicas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Vagotomía , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiología
20.
Cell Metab ; 4(4): 323-31, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17011505

RESUMEN

Ghrelin, a gastrointestinal peptide, stimulates feeding when administered peripherally. Blockade of the vagal afferent pathway abolishes ghrelin-induced feeding, indicating that the vagal afferent pathway may be a route conveying orexigenic ghrelin signals to the brain. Here, we demonstrate that peripheral ghrelin signaling, which travels to the nucleus tractus solitarius (NTS) at least in part via the vagus nerve, increases noradrenaline (NA) in the arcuate nucleus of the hypothalamus, thereby stimulating feeding at least partially through alpha-1 and beta-2 noradrenergic receptors. In addition, bilateral midbrain transections rostral to the NTS, or toxin-induced loss of neurons in the hindbrain that express dopamine beta hydroxylase (an NA synthetic enzyme), abolished ghrelin-induced feeding. These findings provide new evidence that the noradrenergic system is necessary in the central control of feeding behavior by peripherally administered ghrelin.


Asunto(s)
Hipotálamo/metabolismo , Norepinefrina/metabolismo , Hormonas Peptídicas/metabolismo , Rombencéfalo/metabolismo , Transducción de Señal/fisiología , Animales , Dopamina beta-Hidroxilasa/metabolismo , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Ghrelina , Masculino , Neuronas/metabolismo , Neuropéptido Y/metabolismo , Hormonas Peptídicas/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo
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