scholarly journals Cholecystokinin system is involved in the anorexigenic effect of peripherally applied palmitoylated prolactin-releasing peptide in fasted mice

2021 ◽  
pp. 579-590
Author(s):  
Zdenko Pirník ◽  
Lucia Kořínková ◽  
Jana Osacká ◽  
Blanka Železná ◽  
Jaroslav Kuneš ◽  
...  
Keyword(s):  
Food Intake ◽  
Cell Activation ◽  
Hypothalamic Nucleus ◽  
Dependent Manner ◽  
Neuronal System ◽  
Cck1 Receptor ◽  
Neuronal Systems ◽  
Anorexigenic Effect ◽  
Intake Regulation ◽  
Prolactin Releasing Peptide

Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

Possible inhibitory role of prolactin-releasing peptide for ACTH release associated with running stress

2007 ◽  
Vol 292 (1) ◽  
pp. R497-R504 ◽  
Author(s):  
Nao Ohiwa ◽  
Hyukki Chang ◽  
Tsuyoshi Saito ◽  
Tatsushi Onaka ◽  
Takahiko Fujikawa ◽  
...  
Keyword(s):  
Blood Lactate ◽  
Metabolic Response ◽  
Ventrolateral Medulla ◽  
Hypothalamic Nucleus ◽  
Dependent Manner ◽  
Lactate Accumulation ◽  
Blood Lactate Accumulation ◽  
Prolactin Releasing Peptide ◽  
Acth Release

Exercise around the lactate threshold induces a stress response, defined as “running stress.” We have previously demonstrated that running stress is associated with activation of certain regions of the brain, e.g., the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus, that are hypothesized to play an integral role in regulating stress-related responses, including ACTH release during running. Thus we investigated the role of prolactin-releasing peptide (PrRP), found in the ventrolateral medulla and the nucleus of the solitary tract, which is known to project to the PVN during running-induced ACTH release. Accumulation of c-Fos in PrRP neurons correlated with running speeds, reaching maximal levels under running stress. Intracerebroventricular injection of neutralizing anti-PrRP antibodies led to increased plasma ACTH level and blood lactate accumulation during running stress, but not during restraint stress. Exogenous intracerebroventricular administration of low doses of PrRP had the opposite effects. Therefore, our results suggest that, during running stress, PrRP-containing neurons are activated in an exercise intensity-dependent manner, and likewise the produced endogenous PrRP attenuates ACTH release and blood lactate accumulation during running stress. Here we provide a novel perspective on understanding of PrRP in the endocrine-metabolic response associated with running stress.

scholarly journals Prolactin-releasing peptide: a new tool for obesity treatment

2016 ◽  
Vol 230 (2) ◽  
pp. R51-R58 ◽  
Author(s):  
Jaroslav Kuneš ◽  
Veronika Pražienková ◽  
Andrea Popelová ◽  
Barbora Mikulášková ◽  
Jana Zemenová ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Binding Affinity ◽  
Subcutaneous Administration ◽  
Obesity Treatment ◽  
Noninvasive Therapy ◽  
Food Intake Regulation ◽  
Intake Regulation ◽  
Prolactin Releasing Peptide ◽  
The Brain

Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood–brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.

scholarly journals High leptin in pregnant mink (Mustela vison) may exert anorexigenic effects: a permissive factor for rapid increase in food intake during lactation

2004 ◽  
Vol 91 (3) ◽  
pp. 411-421 ◽  
Author(s):  
Anne-Helene Tauson ◽  
Mats Forsberg ◽  
André Chwalibog
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Heat Production ◽  
Plasma Concentrations ◽  
Negative Energy ◽  
Late Gestation ◽  
Negative Energy Balance ◽  
Food Intake Regulation ◽  
Anorexigenic Effect ◽  
Intake Regulation

The role for leptin in food intake regulation in the mink, a polytocous seasonal breeder with altricial young, was investigated in pregnant and lactating dams and data were related to quantitative energy metabolism measurements and plasma concentrations of other important metabolic hormones. A total of nine mink dams were measured in consecutive 1-week balance periods, each including a 22h measurement of heat production by means of indirect calorimetry, and blood was sampled at weekly intervals throughout gestation and during lactation weeks 1–4. Intake of metabolisable energy (ME) was high and energy balance was positive until the first third of true gestation. During mid- and late gestation ME intake decreased (P<0·001) while heat production remained almost constant, resulting in negative energy balance and the loss of body weight. From late gestation until lactation week 4, ME intake increased by 3·5 times, but weight loss continued. Plasma concentrations of leptin were approximately doubled during the last two-thirds of true gestation (P<0·01), demonstrating a clear gestational hyperleptinaemia. Concentrations declined rapidly after parturition and then remained stable. Insulin was independent of leptin, with low concentrations coincident with hyperleptinaemia. Also, concentrations of thyroid hormones declined during gestation, probably reflecting the low food intake. Hyperleptinaemia concomitant with low ME intake, negative energy balance and mobilisation of body reserves suggested an anorexigenic effect of leptin in pregnant mink. This suppression of food intake in late gestation might be permissive for the rapid increase in food intake occurring after parturition.

scholarly journals Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

2021 ◽  
Author(s):  
Kengo Inada ◽  
Kazuko Tsujimoto ◽  
Masahide Yoshida ◽  
Katsuhiko Nishimori ◽  
Kazunari Miyamichi
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Neural Circuit ◽  
Intraperitoneal Administration ◽  
Whole Body ◽  
Hypothalamic Nucleus ◽  
Physiological Regulation ◽  
Hypothalamic Regulation ◽  
Obesity In Mice ◽  
Anorexigenic Effect

Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (OT) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. OT has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of OT signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of OT or OT receptor (OTR) has little effect on food intake. We herein show that acute conditional KO (cKO) of OT selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of OT rescues the hyperphagic phenotype of the PVH OT cKO model. Furthermore, we show that cKO of OTR selectively in the posterior hypothalamic regions, which include the primary centers for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data functionally reveal that OT signaling in the posterior hypothalamic regions suppresses excessive food intake.

Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

1990 ◽  
Vol 48 (3) ◽  
pp. 952-953
Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard
Keyword(s):  
Adrenal Medulla ◽  
Calcium Binding ◽  
Chromaffin Cells ◽  
Cell Activation ◽  
Structural Information ◽  
Dependent Manner ◽  
Chromaffin Granules ◽  
Immuno Electron Microscopy ◽  
Ultrathin Sections ◽  
Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

scholarly journals Actin Depolymerization Transduces the Strength of B-Cell Receptor Stimulation

2005 ◽  
Vol 16 (5) ◽  
pp. 2275-2284 ◽  
Author(s):  
Shengli Hao ◽  
Avery August
Keyword(s):  
B Cell ◽  
Lipid Raft ◽  
Cell Activation ◽  
Cell Receptor ◽  
Dependent Manner ◽  
B Cell Activation ◽  
Erk Activation ◽  
Actin Depolymerization ◽  
Transcription Factor Activation ◽  
Raft Clustering

Polymerization of the actin cytoskeleton has been found to be essential for B-cell activation. We show here, however, that stimulation of BCR induces a rapid global actin depolymerization in a BCR signal strength-dependent manner, followed by polarized actin repolymerization. Depolymerization of actin enhances and blocking actin depolymerization inhibits BCR signaling, leading to altered BCR and lipid raft clustering, ERK activation, and transcription factor activation. Furthermore actin depolymerization by itself induces altered lipid raft clustering and ERK activation, suggesting that F-actin may play a role in separating lipid rafts and in setting the threshold for cellular activation.

scholarly journals CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

2021 ◽  
Vol 22 (10) ◽  
pp. 5394
Author(s):  
Tomas Lidak ◽  
Nikol Baloghova ◽  
Vladimir Korinek ◽  
Radislav Sedlacek ◽  
Jana Balounova ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Ubiquitin Ligase ◽  
Cell Activation ◽  
Rna Helicase ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Risc Complex ◽  
Wide Range

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

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