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1.
Biochem Biophys Res Commun ; 534: 653-658, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33228964

RESUMO

Two novel peptides, neuromedin U precursor-related peptide (NURP) and neuromedin S precursor-related peptide (NSRP), are produced from neuromedin U (NMU) and neuromedin S (NMS) precursors, respectively, as these precursors have multiple consensus sequences for proteolytic processing. Our group has shown previously that one of these two novel peptides, NURP, stimulates body temperature and locomotor activity, but not food intake. However, the physiological function of the other peptide, NSRP, has remained unclear. Therefore, the aim of this study was to characterize differences in the regions of the rat brain targeted by the NMU/NMS peptide family, including NURP and NSRP, and their physiological functions. First, we explored the regions of c-Fos expression after intracerebroventricular (i.c.v.) injection of NURP and NSRP and found that these were fewer than after i.c.v. injection of NMU and NMS in the hypothalamus, possibly because NURP and NSRP cannot activate NMU/NMS receptors. In the ventral subiculum, which is one region of the hippocampus, c-Fos expression was evident only after i.c.v. injection of NURP. We also examined the effects of NSRP on food intake, body temperature and locomotor activity. Like NURP, NSRP increased both body temperature and locomotor activity, but not food intake, indicating that NSRP is also a functional peptide. However, these effects of NSRP were distinctly weaker than those of NURP. These findings suggest differences in the affinity of NURP and/or NSRP for specific receptors, or in their respective biological activities.


Assuntos
Sistema Nervoso Central/fisiologia , Neuropeptídeos/fisiologia , Precursores de Proteínas/fisiologia , Sequência de Aminoácidos , Animais , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Injeções Intraventriculares , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Neuropeptídeos/administração & dosagem , Neuropeptídeos/genética , Precursores de Proteínas/administração & dosagem , Precursores de Proteínas/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Receptores de Neurotransmissores/fisiologia , Homologia de Sequência de Aminoácidos
2.
Biochem Biophys Res Commun ; 521(2): 521-526, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31677791

RESUMO

Neuromedin U (NMU) has a precursor that contains one additional peptide consisting of 33 or 36 amino acid residues. Recently, we identified this second peptide from rat brain and designated it neuromedin U precursor-related peptide (NURP), showing it to stimulate prolactin release from the pituitary when injected via the intracerebroventricular (icv) route. Here, we examined whether NMU, like NURP, also stimulates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pituitary. This suppression of prolactin release by NMU was observed in hyper-prolactin states such as lactation, stress, pseudopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. Immunohistochemical analysis revealed that icv injection of NMU induced cFos expression in dopaminergic neurons of the arcuate nucleus, but not the substantia nigra. Mice with double knockout of NMU and neuromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These results suggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.


Assuntos
Núcleo Arqueado do Hipotálamo/citologia , Neurônios Dopaminérgicos/metabolismo , Neuropeptídeos/fisiologia , Prolactina/metabolismo , Animais , Camundongos , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Receptores de Neurotransmissores
3.
Biochem Biophys Res Commun ; 517(3): 433-438, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31376933

RESUMO

Neuromedin U (NMU) plays important roles in energy homeostasis in rodents and birds. Previously, our group has isolated four cDNAs encoding precursor proteins of NMU from the goldfish brain and gut, and it was assumed that these transcripts are produced by alternative splicing. We have also demonstrated that intracerebroventricular (ICV) injection of putative goldfish NMU inhibits food intake. However, as native goldfish NMU has not yet been identified, we attempted to purify it from goldfish brain and gut extracts. To assess NMU activity in fractions at each purification step, we measured changes in the intracellular concentrations of Ca2+ using HEK293 cells expressing goldfish NMU-R1 or -R2. We isolated a 25-amino-acid peptide (NMU-25) from the brain and gut and found that its primary structure is similar to that of mammalian NMU. Another 21-amino-acid peptide (NMU-21) was purified from the brain, but not from the gut. Furthermore, a 9-amino-acid peptide (NMU-9) identical to the C-terminus of NMU-21 and -25 was also isolated from the brain and gut. Treatment with synthetic NMU-9, -21 and -25 dose-dependently increased the intracellular Ca2+ concentration in mammalian cells expressing goldfish NMU-R1 and -R2. We also examined the effect of ICV-administered synthetic goldfish NMUs on goldfish food intake. NMU-25 inhibited food intake to the same degree as NMU-21. However, the inhibitory effect of NMU-9 was slightly weaker than those of NMU-21 and -25. These results indicate that several molecular forms of NMU exist in the goldfish brain and gut, and that all of them play physiological roles via NMU-R1 and NMU-R2.


Assuntos
Encéfalo/metabolismo , Proteínas de Peixes/genética , Trato Gastrointestinal/metabolismo , Carpa Dourada/genética , Neuropeptídeos/genética , Receptores de Neurotransmissores/genética , Sequência de Aminoácidos , Animais , Transporte Biológico , Cálcio/metabolismo , Galinhas , Ingestão de Alimentos/fisiologia , Feminino , Proteínas de Peixes/isolamento & purificação , Proteínas de Peixes/metabolismo , Proteínas de Peixes/farmacologia , Expressão Gênica , Carpa Dourada/metabolismo , Células HEK293 , Humanos , Masculino , Neuropeptídeos/isolamento & purificação , Neuropeptídeos/metabolismo , Neuropeptídeos/farmacologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/isolamento & purificação , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacologia , Ratos , Receptores de Neurotransmissores/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transgenes
4.
J Vet Med Sci ; 81(9): 1305-1312, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31341114

RESUMO

Recently, it has been proposed that neuromedin U (NMU) is "decretin", which suppresses insulin secretion from the pancreas in vitro. Here we examined the possible involvement of NMU in insulin secretion in vivo by comparing the plasma glucose and insulin levels of wild-type mice with those of double knockout (D-KO) of the NMU and neuromedin S (NMS) genes, as NMS binds to the neuromedin U receptor. If NMU is, in fact, "decretin", which inhibits insulin secretion from the pancreas, then NMU-deficient mice might result in higher plasma insulin levels than is the case in wild-type mice, or injection of NMU lead to suppression of plasma insulin level. In this study, we found that the fasting plasma level of insulin was not increased in D-KO mice. Glucose tolerance tests revealed no significant difference in plasma insulin levels between wild-type mice and D-KO mice under non-fasting conditions. After peripheral injection of NMU, plasma glucose and insulin levels did not show any significant changes in either wild-type or D-KO mice. Glucose tolerance testing after 3 weeks of high fat feeding revealed no significant difference in plasma insulin levels during 60 min after glucose injection between wild-type and D-KO mice. These results suggest that even if NMU is a decretin candidate, its physiological involvement in suppression of insulin secretion may be very minor in vivo.


Assuntos
Glicemia/efeitos dos fármacos , Insulina/sangue , Neuropeptídeos/genética , Animais , Dieta Hiperlipídica , Teste de Tolerância a Glucose , Secreção de Insulina/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuropeptídeos/farmacologia
5.
Food Funct ; 10(1): 38-48, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30548041

RESUMO

Natural killer (NK) cells play an important role in the innate immune system by eliminating cancer cells and virally infected cells. Aging and stress attenuate the activity of NK cells, thereby increasing the risk of various diseases. In this study, we demonstrated that the consumption of a small number of kumquats in an in vivo model could suppress elevated plasma corticosterone levels and reverse the decline in splenocyte cytotoxicity caused by restraint stress. Our results identified ß-cryptoxanthin (BCX) as an active kumquat component with a NK cell-activating effect, and R-limonene as an active component that mediates not only the anti-stress effect but also NK cell activation by oral administration. In addition, BCX, R-limonene, and R-limonene metabolites were found to enhance IFN-γ production in KHYG-1 cells, a human NK cell line. Collectively, our findings suggest that the ingestion of a few kumquats on a daily basis can help to combat stress and enhance NK cell activity.


Assuntos
Adjuvantes Imunológicos/metabolismo , beta-Criptoxantina/metabolismo , Limoneno/metabolismo , Extratos Vegetais/metabolismo , Rutaceae/metabolismo , Adjuvantes Imunológicos/química , Animais , beta-Criptoxantina/química , Linhagem Celular , Corticosterona/sangue , Humanos , Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Limoneno/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Rutaceae/química , Estresse Fisiológico
6.
Sci Rep ; 7(1): 10468, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28874765

RESUMO

The discovery of neuropeptides provides insights into the regulation of physiological processes. The precursor for the neuropeptide neuromedin U contains multiple consensus sequences for proteolytic processing, suggesting that this precursor might generate additional peptides. We performed immunoaffinity chromatography of rat brain extracts and consequently identified such a product, which we designated neuromedin U precursor-related peptide (NURP). In rat brain, NURP was present as two mature peptides of 33 and 36 residues. Radioimmunoassays revealed NURP immunoreactivity in the pituitary, small intestine, and brain of rats, with the most intense reactivity in the pituitary. Intracerebroventricular administration of NURP to both male and female rats robustly increased plasma concentrations of prolactin but not of other anterior pituitary hormones. In contrast, NURP failed to stimulate prolactin release from dispersed anterior pituitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sulpiride, intracerebroventricular administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data suggest that NURP induces prolactin release by acting indirectly on the pituitary; dopamine from the hypothalamus, which inhibits prolactin release, may be involved in this activity of NURP.


Assuntos
Neuropeptídeos/metabolismo , Prolactina/biossíntese , Precursores de Proteínas/metabolismo , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Imuno-Histoquímica , Masculino , Neuropeptídeos/química , Neuropeptídeos/isolamento & purificação , Precursores de Proteínas/química , Proteólise , Ratos , Receptores Dopaminérgicos/metabolismo
7.
Biochem Biophys Res Commun ; 492(3): 412-418, 2017 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-28843854

RESUMO

It has been suggested that novel peptide that is produced from the neuromedin U (NMU) precursor may exist, as this precursor contains multiple consensus sequences for proteolytic processing. Recently, we identified two mature novel peptides comprising 33 and 36 residues in the rat brain, which were designated neuromedin U precursor-related peptide (NURP) 33 and 36. In the present study, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. Immunoreactivity for NMU and NURPs was widely present in the central nervous system and showed a similar distribution. Intracerebroventricular (icv) injection of NURP33 in rats increased locomotor activity, energy expenditure, heart rate and back surface temperature (BS-T), similarly to NMU or NURP36. NMU treatment reduced food intake, but NURP33 did not. Pretreatment with the ß3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-induced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamus and for uncoupling protein 1 in the brown adipose tissue. These results suggest that although NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.


Assuntos
Neuropeptídeos/química , Neuropeptídeos/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Ingestão de Alimentos/efeitos dos fármacos , Indometacina/farmacologia , Infusões Intraventriculares , Masculino , Propanolaminas/farmacologia , Ratos , Ratos Wistar
8.
Life Sci ; 182: 73-79, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28625358

RESUMO

AIMS: We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury. MAIN METHODS: XOR+/+ and XOR+/- mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining. KEY FINDINGS: The BUN and Cr concentrations in the XOR+/+IR mice were increased significantly compared to those in XOR+/-IR and allopurinol-treated XOR+/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR+/+IR and XOR+/-IR mice compared to the XOR+/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR+/+IR mice compared to those in the XOR+/-IR mice. The histological analysis revealed that the XOR+/-IR and allopurinol-treated XOR+/+IR mice showed less tubular injury than the XOR+/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine. SIGNIFICANCE: Both the disruption of XOR gene in XOR+/- mice and the reduction of XOR activity in allopurinol-treated XOR+/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target.


Assuntos
Alopurinol/farmacologia , Nefropatias/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Xantina Desidrogenase/genética , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Inflamação/genética , Inflamação/patologia , Nefropatias/genética , Masculino , Camundongos , Camundongos Knockout , Estresse Oxidativo/genética , Traumatismo por Reperfusão/genética , Xantina Desidrogenase/antagonistas & inibidores
9.
J Vet Med Sci ; 79(7): 1284-1293, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-28652558

RESUMO

The C57BL/6J-Daruma mouse is an animal model of obesity derived from the original genetically obese ICR-Daruma mouse by transfer of the phenotype into the C57BL/6J background by backcrossing into the C57BL/6J strain. Although, like the original ICR-Daruma mouse model, both male and female C57BL/6J-Daruma mice develop obesity, the latter strain shows sex differences in several phenotypes. A sex difference in plasma insulin levels was especially notable in C57BL/6J-Daruma mice; only males showed hyperinsulinemia. Orchiectomy suppressed this hyperinsulinemia completely, whereas testosterone supplementation restored it. Glucose administration increased the plasma glucose level in both male and female Daruma mice to a greater extent than in wild-type control mice. Orchiectomy, but not ovariectomy, decreased the plasma glucose level to that seen in wild-type controls. On the other hand, this effect of orchiectomy was abrogated by testosterone supplementation. The expression of mRNAs for several genes related to insulin resistance was significantly changed in white adipose tissue and liver of C57BL/6J-Daruma mice, especially males, as early as 4 weeks of age. The present results suggest that testosterone may be involved in the hyperinsulinemia shown by male C57BL/6J-Daruma mice and that this strain may be an appropriate animal model for examining the relationship between obesity and sex hormones.


Assuntos
Hiperinsulinismo/veterinária , Camundongos Endogâmicos C57BL/fisiologia , Camundongos Obesos/fisiologia , Tecido Adiposo Branco/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Fígado/metabolismo , Masculino , Camundongos , Orquiectomia/veterinária , Ovariectomia/veterinária , Fatores Sexuais
10.
Neuropeptides ; 65: 21-27, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28433253

RESUMO

The central role of neuropeptide S (NPS), identified as the endogenous ligand for GPR154, now named neuropeptide S receptor (NPSR), has not yet been fully clarified. We examined the central role of NPS for body temperature, energy expenditure, locomotor activity and adrenal hormone secretion in rats. Intracerebroventricular (icv) injection of NPS increased body temperature in a dose-dependent manner. Energy consumption and locomotor activity were also significantly increased by icv injection of NPS. In addition, icv injection of NPS increased the peripheral blood concentration of adrenalin and corticosterone. Pretreatment with the ß1- and ß2-adrenergic receptor blocker timolol inhibited the NPS-induced increase of body temperature. The expression of both NPS mRNA in the brainstem and NPSR mRNA in the hypothalamus showed a nocturnal rhythm with a peak occurring during the first half of the dark period. To examine whether the endogenous NPS is involved in regulation of body temperature, NPSR antagonist SHA68 was administered one hour after darkness. SHA68 attenuated the nocturnal rise of body temperature. These results suggest that NPS contributes to the regulation of the sympathetic nervous system.


Assuntos
Atividade Motora , Neuropeptídeos/fisiologia , Sistema Nervoso Simpático/fisiologia , Termogênese , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Tronco Encefálico/metabolismo , Ritmo Circadiano , Corticosterona/sangue , Metabolismo Energético , Epinefrina/sangue , Hipotálamo/metabolismo , Masculino , Neuropeptídeos/administração & dosagem , Oxazolidinonas/administração & dosagem , Pirazinas/administração & dosagem , RNA Mensageiro/metabolismo , Ratos Wistar , Receptores de Neuropeptídeos/antagonistas & inibidores
11.
Hypertension ; 69(1): 143-153, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27872234

RESUMO

Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca2+-activated K+ channels (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that Ca2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SKCa/IKCa in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IKCa, using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SKCa/IKCa blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SKCa activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SKCa protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IKCa were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SKCa input to EDH.


Assuntos
Regulação para Baixo , Endotélio Vascular/metabolismo , Hipertensão/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Canais de Cátion TRPV/genética , Vasodilatação , Animais , Western Blotting , DNA/genética , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Artérias Mesentéricas/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Canais de Potássio Ativados por Cálcio de Condutância Baixa/biossíntese , Canais de Cátion TRPV/biossíntese
12.
Neurosci Lett ; 615: 28-32, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26773867

RESUMO

We have shown previously that des-acyl ghrelin decreases body temperature in rats through activation of the parasympathetic nervous system. Here we investigated whether des-acyl ghrelin ameliorates heatstroke in rats exposed to high temperature. Peripheral administration of des-acyl ghrelin significantly attenuated hyperthermia induced by exposure to high-temperature (35°C) together with high humidity (70-80%). Although biochemical analysis revealed that exposure to high temperature significantly increased hematocrit and the serum levels of aspartate amino transferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine and electrolytes (Na(+), K(+), Cl(-)), most of these heatstroke-associated reactions were significantly reduced by treatment with des-acyl ghrelin. The level of des-acyl ghrelin in plasma was also found to be significantly increased under high-temperature conditions. These results suggest that des-acyl ghrelin could be useful for preventing heatstroke under high temperature condition.


Assuntos
Grelina/uso terapêutico , Golpe de Calor/prevenção & controle , Temperatura Alta/efeitos adversos , Umidade/efeitos adversos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Temperatura Corporal/efeitos dos fármacos , Cloretos/sangue , Creatinina/sangue , Eletrólitos , Grelina/sangue , Golpe de Calor/etiologia , Golpe de Calor/fisiopatologia , Hematócrito , Masculino , Potássio/sangue , Ratos Wistar , Sódio/sangue
13.
Biochem Biophys Res Commun ; 470(4): 930-5, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26826380

RESUMO

We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the ß3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and ß3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU.


Assuntos
Tecido Adiposo Marrom/fisiologia , Regulação da Temperatura Corporal/fisiologia , Hipotálamo/fisiologia , Neuropeptídeos/metabolismo , Animais , Masculino , Camundongos , Camundongos Knockout , Ratos , Ratos Wistar
14.
J Vet Med Sci ; 77(7): 815-21, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25787929

RESUMO

We measured the plasma levels of amino acids at various reproductive stages in female rats, including the estrous cycle, pregnancy and lactation, and compared the resulting amino acid profiles using two- or three-dimensional figures. These figures revealed that the amino acid profiles of pregnant and lactating dams differed considerably from those during the estrous cycle or in male rats. The plasma levels of individual amino acids were almost the same between proestrus, estrus, metestrus and diestrus, and their profiles did not differ significantly. However, the amino acid profiles changed during pregnancy and lactation in dams. The plasma Ser level decreased significantly in mid and late pregnancy, whereas Tyr, Gly and His decreased significantly in the late and end stages of pregnancy, and Trp and Lys significantly decreased and increased at the end of pregnancy, respectively. Much larger changes in amino acid profiles were observed during lactation, when the levels of many amino acids increased significantly, and none showed a significant decrease. Plasma Pro, Ser and Gly levels increased continuously from day 1 until day 15 of lactation, whereas Asn and Met increased significantly from days 1 and 5 respectively until the end of lactation. These results suggest that the profiles of plasma amino acids show characteristic changes according to reproductive stage and that it may be necessary to consider such differences when performing amino acid-based diagnosis.


Assuntos
Aminoácidos/sangue , Ciclo Estral/sangue , Lactação/sangue , Prenhez/sangue , Ratos/sangue , Aminoácidos/fisiologia , Animais , Ciclo Estral/fisiologia , Estro/sangue , Estro/fisiologia , Feminino , Lactação/fisiologia , Masculino , Metestro/sangue , Metestro/fisiologia , Gravidez , Prenhez/fisiologia , Proestro/sangue , Proestro/fisiologia , Ratos/fisiologia , Ratos Wistar
15.
J Vet Med Sci ; 77(6): 661-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25715957

RESUMO

It has been suspected that in comparison with glucose or fatty acids, the levels of amino acids may readily change with different forms of exercise. In the present study, we measured the concentrations of amino acids, glucose, triglycerides, total protein and total cholesterol in the blood and/or cerebrospinal fluid (CSF) of rats subjected to forced running exercise on a treadmill, and voluntary running exercise using a wheel, with a constant running distance of 440 m. Rats that performed no running and rats subjected to immobilization stress were used as controls. We observed a few significant changes in the levels of plasma glucose, triglycerides, total protein and total cholesterol in all groups. Whereas, plasma amino acid levels were significantly changed by exercise and stress, especially during the light period. The plasma levels of many amino acids were specifically increased by forced running; some were decreased by immobilization stress. Few amino acids showed similar changes in their levels as a result of voluntary running. In addition, there was a significant difference in the degree of amino acid imbalance between blood and CSF. These results provide the first information on changes in levels of amino acids in plasma and CSF resulting from forced and voluntary exercises.


Assuntos
Aminoácidos/sangue , Condicionamento Físico Animal/fisiologia , Corrida/fisiologia , Estresse Psicológico/fisiopatologia , Aminoácidos/líquido cefalorraquidiano , Análise de Variância , Animais , Glicemia/metabolismo , Proteínas Sanguíneas/metabolismo , Proteínas do Líquido Cefalorraquidiano/metabolismo , Colesterol/sangue , Colesterol/líquido cefalorraquidiano , Cromatografia Líquida , Glucose/líquido cefalorraquidiano , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Triglicerídeos/sangue , Triglicerídeos/líquido cefalorraquidiano
16.
Neurol Med Chir (Tokyo) ; 54(7): 511-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24305024

RESUMO

The supplementary motor area (SMA) is a key structure involved in behavioral planning and execution. Although many reports have indicated that SMA is organized somatotopically, its exact organization remains still unclear. This study aimed to functionally map SMA using functional magnetic resonance imaging (fMRI) and validate the fMRI-SMA by electrocortical stimulation (ECS) and postsurgical symptoms. Total 32 healthy volunteers and 24 patients participated in this study. Motor tasks were right and left finger tapping and language tasks included simple reading, lexical decision for presented words, and verb generating tasks. SPM8 was used to conduct individual and group analyses. In all subjects, the lexical decision task induced the greatest number of active fMRI pixels in SMA. fMRI during the language tasks showed anterior part of SMA compared to finger tapping tasks. We found an overlap spot with all different tasks in posterior part of SMA, which we termed SMA core. Six patients underwent awake craniotomy for ECS mapping for primary regions and SMA. During awake craniotomy, ECS to posterior part of SMA, which might involve the possible SMA core consistently, evoked both speech arrest and flaccid hemiparesis. The SMA mapping suggested posterior part of SMA might play more important roles in any executions, which might involve the SMA core.


Assuntos
Comportamento/fisiologia , Mapeamento Encefálico/métodos , Eletrocorticografia , Imageamento por Ressonância Magnética , Córtex Motor/fisiopatologia , Adulto , Idoso , Craniotomia , Tomada de Decisões/fisiologia , Dominância Cerebral/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Leitura , Valores de Referência , Fala/fisiologia , Comportamento Verbal/fisiologia , Aprendizagem Verbal/fisiologia
17.
J Mol Endocrinol ; 52(2): 97-109, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24299740

RESUMO

The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.


Assuntos
Apetite/genética , Núcleo Arqueado do Hipotálamo/metabolismo , Lactação/genética , Neuropeptídeos/genética , Tecido Adiposo Branco/metabolismo , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Animais , Peso Corporal/genética , Colecistocinina/genética , Colecistocinina/metabolismo , Ingestão de Alimentos/genética , Feminino , Lactação/sangue , Leptina/sangue , Masculino , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Tamanho do Órgão/genética , Gravidez , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
18.
Arterioscler Thromb Vasc Biol ; 34(1): 44-51, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24158515

RESUMO

OBJECTIVE: Xanthine oxidoreductase (XOR) catalyzes the production of uric acid with concomitant generation of reactive oxygen species. XOR has been shown to regulate adipogenesis through the control of peroxisome proliferator-activated receptor γ, but its role in adipose tissue remains unclear. The aim of this study was to examine the role of XOR in adipose tissue using XOR genetically modified mice. APPROACH AND RESULTS: Experiments were performed using 2-, 4-, and 18-month-old XOR heterozygous mice (XOR(+/-)) and their wild-type littermates to evaluate the physiological role of XOR as the mice aged. Stromal vascular fraction cells were prepared from epididymal white adipose tissue in 2-month-old XOR mice to assess adipogenesis. At 18 months, XOR(+/)- mice had significantly higher body weight, higher systolic blood pressure, and higher incidence of insulin resistance compared with wild-type mice. At 4 months, blood glucose and the expressions of CCAAT enhancer-binding protein ß, peroxisome proliferator-activated receptor γ, monocyte chemoattractant protein-1, and tumor necrosis factor α mRNA in epididymal white adipose tissue were significantly higher in XOR(+/-) than in wild-type mice. Furthermore, histological analysis of epididymal white adipose tissue in XOR(+/-) mice revealed that adipocyte size and the F4/80-positive macrophage count were increased. Experiments with a high-fat diet exhibited that body weight gain was also significantly higher in XOR(+/-) than in wild-type mice. In stromal vascular fraction cells derived from XOR(+/-) mice, the levels of peroxisome proliferator-activated receptor γ, fatty acid-binding protein 4, and CCAAT enhancer-binding protein α mRNA were upregulated, and oxidative stress levels were elevated during differentiation into adipocytes. CONCLUSIONS: These results suggest that the reduction in XOR gene expression in mice augments lipid accumulation in adipocytes, accompanied by an increase in oxidative stress, and induces obesity with insulin resistance in older age.


Assuntos
Adipócitos/enzimologia , Adipogenia , Tecido Adiposo Branco/enzimologia , Heterozigoto , Metabolismo dos Lipídeos , Obesidade/enzimologia , Xantina Desidrogenase/deficiência , Adipócitos/patologia , Tecido Adiposo Branco/patologia , Fatores Etários , Animais , Glicemia/metabolismo , Pressão Sanguínea , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Resistência à Insulina , Masculino , Camundongos , Camundongos Knockout , Obesidade/genética , Obesidade/patologia , Obesidade/fisiopatologia , Estresse Oxidativo , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Aumento de Peso , Xantina Desidrogenase/genética
19.
FASEB J ; 28(1): 131-42, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24022401

RESUMO

Proliferative vitreoretinopathy (PVR) is a severe, vision-threatening disorder characterized by the fibrous membrane formation that leads to tractional retinal detachment. There has been no effective therapeutic approach other than vitreoretinal surgery. In this study, DNA microarray analysis of the fibrous membranes revealed significant up-regulation of periostin. We also found increased periostin expression in the vitreous and retinal pigment epithelial (RPE) cells from fibrous membranes of PVR patients. In vitro, periostin increased proliferation, adhesion, migration, and collagen production in RPE cells through integrin αV-mediated FAK and AKT phosphorylation. Periostin blockade suppressed migration and adhesion induced by TGFß2 and PVR vitreous. In vivo, periostin inhibition had the inhibitory effect on progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells. These results identified periostin as a pivotal molecule for fibrous membrane formation as well as a promising therapeutic target for PVR.


Assuntos
Moléculas de Adesão Celular/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia , Adulto , Idoso , Animais , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Eletrorretinografia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Circ J ; 77(12): 3015-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24088305

RESUMO

BACKGROUND: Velocity-encoded cine magnetic resonance imaging (VEC-MRI) has recently been reported as effective for assessing not only pulmonary blood flow (Qp) but also pulmonary arterial pressure (PAP) in adults. However, there have been few reports on the usefulness of VEC-MRI for assessing PAP in children with congenital heart disease (CHD). METHODS AND RESULTS: We evaluated 34 children with CHD. Qp and systemic blood flows (Qs) were determined by cardiac catheterization and VEC-MRI. The right-to-left Qp ratio (R/L) was measured by pulmonary perfusion scintigraphy and VEC-MRI. The pulmonary-to-systemic blood pressure ratio (Pp/Ps) was determined by cardiac catheterization. The acceleration time (AcT), ejection time (ET), peak velocity (PV), acceleration volume (AcV), and maximal change in flow rate during ejection (MCFR) in the pulmonary arteries, which were standardized by body surface area, were determined by VEC-MRI. The children were divided into 2 groups according to Pp/Ps. The Qs, R/L ratio and Qp/Qs obtained by VEC-MRI strongly correlated with those obtained by catheterization and scintigraphy. No significant differences in AcT, ET, AcT/ET, PV, or AcV were observed between the 2 groups. However, a significant difference was observed in MCFR. Furthermore, a significant correlation was observed between the MCFR and Pp/Ps. CONCLUSIONS: This study clearly demonstrated that VEC-MRI is useful for assessing not only blood flow, but also PAP, by referring to MCFR in children.


Assuntos
Pressão Sanguínea , Cardiopatias Congênitas , Angiografia por Ressonância Magnética , Artéria Pulmonar , Velocidade do Fluxo Sanguíneo , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Radiografia
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