Increased ACTH response to corticotropin-releasing factor in cold-adapted rats in vivo

1989 ◽  
Vol 257 (3) ◽  
pp. E336-E339 ◽  
Author(s):  
A. Uehara ◽  
Y. Habara ◽  
A. Kuroshima ◽  
C. Sekiya ◽  
Y. Takasugi ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cold Adaptation ◽  
Corticotropin Releasing Factor ◽  
Plasma Acth ◽  
Cold Adapted ◽  
Repeated Restraint Stress ◽  
Cross Adaptation ◽  
Freely Moving ◽  
Increased Activity

We have recently reported that chronically repeated restraint stress results in improved cold tolerance in rats via an increased activity of nonshivering thermogenesis, a characteristic metabolic change observed during cold adaptation, suggesting the presence of cross-adaptation between cold and stress. It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is activated in various stress responses. In the present study, therefore, we examined whether cold adaptation would alter the adrenocorticotropic hormone (ACTH)-releasing state in vivo using freely moving, conscious rats chronically implanted with intra-atrial cannulas. There was no difference in the basal levels of plasma ACTH between warm control and cold-adapted rats. On the other hand, the ACTH response to the intravenous administration of corticotropin-releasing factor (CRF; 2 micrograms/animal) was significantly elevated in cold-adapted rats. However, the injection of 10 micrograms of CRF, which was considered as a dose to elicit the maximal ACTH response, resulted in similar ACTH release patterns between the two groups. These changes in the responsiveness of ACTH secretion have been observed in rats chronically exposed to stressful conditions. The results demonstrated in the present study, therefore, provide further evidence for our hypothesis that there may exist cross-adaptation between cold and nonthermal stress.

scholarly journals Actin cytoskeleton–dependent regulation of corticotropin-releasing factor receptor heteromers

2017 ◽  
Vol 28 (18) ◽  
pp. 2386-2399 ◽  
Author(s):  
Burcu Hasdemir ◽  
Shilpi Mahajan ◽  
Juan Oses-Prieto ◽  
Shreya Chand ◽  
Michael Woolley ◽  
...  
Keyword(s):  
Stress Responses ◽  
G Protein Coupled Receptors ◽  
Corticotropin Releasing Factor ◽  
Regulatory Proteins ◽  
Hek293 Cells ◽  
Receptor Heteromers ◽  
Class B ◽  
G Protein Coupled ◽  
Stimulation Of

Stress responses are highly nuanced and variable, but how this diversity is achieved by modulating receptor function is largely unknown. Corticotropin-releasing factor receptors (CRFRs), class B G protein–coupled receptors, are pivotal in mediating stress responses. Here we show that the two known CRFRs interact to form heteromeric complexes in HEK293 cells coexpressing both CRFRs and in vivo in mouse pancreas. Coimmunoprecipitation and mass spectrometry confirmed the presence of both CRF1R and CRF2βR, along with actin in these heteromeric complexes. Inhibition of actin filament polymerization prevented the transport of CRF2βR to the cell surface but had no effect on CRF1R. Transport of CRF1R when coexpressed with CRF2βR became actin dependent. Simultaneous stimulation of cells coexpressing CRF1R+CRF2βR with their respective high-affinity agonists, CRF+urocortin2, resulted in approximately twofold increases in peak Ca2+responses, whereas stimulation with urocortin1 that binds both receptors with 10-fold higher affinity did not. The ability of CRFRs to form heteromeric complexes in association with regulatory proteins is one mechanism to achieve diverse and nuanced function.

scholarly journals Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents

2015 ◽  
Vol 114 (6) ◽  
pp. 3339-3350 ◽  
Author(s):  
Avraham M. Libster ◽  
Ben Title ◽  
Yosef Yarom
Keyword(s):  
Firing Rate ◽  
Stress Responses ◽  
Sodium Current ◽  
Ionic Currents ◽  
Corticotropin Releasing Factor ◽  
Voltage Dependent ◽  
Biophysical Mechanism ◽  
The Central Nervous System ◽  
Firing Properties

Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acute rat cerebellar slices. CRF increased the PN firing rate, regardless of whether they were firing tonically or switching between firing and quiescent periods. Current- and voltage-clamp experiments showed that the increase in firing rate was associated with a voltage shift of the activation curve of the persistent sodium current and hyperpolarizing-activated current, as well as activation of voltage-dependent potassium current. The multiple effects on various ionic currents, which are in agreement with the possibility that activation of CRF receptors triggers several intracellular pathways, are manifested as an increase excitability of PN.

scholarly journals Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

2021 ◽  
Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  
Keyword(s):  
Eyeblink Conditioning ◽  
Pyramidal Cells ◽  
Conditioned Eyeblink ◽  
Cellular Mechanisms ◽  
Sustained Activity ◽  
Early Acquisition ◽  
Freely Moving ◽  
Trace Eyeblink Conditioning

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

scholarly journals Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

2021 ◽  
Vol 7 (3) ◽  
pp. 163 ◽  
Author(s):  
Sabelle Jallow ◽  
Nelesh P. Govender
Keyword(s):  
Pathogenic Fungi ◽  
Candida Spp ◽  
Fungal Cell ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Synthase Inhibitor ◽  
Increased Activity ◽  
In Vitro Data

Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug–drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.

scholarly journals Methane and Inflammation - A Review (Fight Fire with Fire)

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Marietta Zita Poles ◽  
László Juhász ◽  
Mihály Boros
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Signalling Pathways ◽  
Experimental Conditions ◽  
Neuroprotective Effects ◽  
Oxidative And Nitrosative Stress ◽  
Carbohydrate Fermentation ◽  
Insight Into

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

Effects of a primary immune response to T-cell dependent antigen on serotonin metabolism in frontal cortex: in vivo microdialysis study in freely moving Fischer 344 rat

1994 ◽  
Vol 645 (1-2) ◽  
pp. 150-156 ◽  
Author(s):  
Alain M. Gardier ◽  
Sébastien Kachaner ◽  
Elisabeth Khan Shaghaghi ◽  
Christian Blot ◽  
Claude Bohuon ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Vivo Microdialysis ◽  
Primary Immune Response ◽  
Serotonin Metabolism ◽  
Fischer 344 ◽  
Fischer 344 Rat ◽  
Freely Moving ◽  
Microdialysis Study

The Effects of Thyroxine and Isopropylnoradrenaline on Cytochrome Oxidase Activity in Brown Adipose Tissue

1973 ◽  
Vol 51 (10) ◽  
pp. 751-758 ◽  
Author(s):  
H. M. C. Heick ◽  
C. Vachon ◽  
Mary Ann Kallai ◽  
Nicole Bégin-Heick ◽  
J. LeBlanc
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Cytochrome Oxidase ◽  
Cold Adaptation ◽  
Metabolic Response ◽  
Mitochondrial Enzymes ◽  
Cold Adapted ◽  
Brown Adipose ◽  
Hormonal Treatments

Groups of animals were treated with injections of isopropylnoradrenaline, thyroxine, or both hormones together. The effects of these hormonal treatments on the size, protein content, and level of some mitochondrial enzymes, in particular the cytochrome oxidase, were determined and compared to the effect on these parameters produced by cold adaptation. The changes observed were correlated with the resistance of the animals to cold stress and with their metabolic response to injections of isopropylnoradrenaline. All treatments increased the size of the brown adipose tissue. Whereas thyroxine had little effect on the protein content and cytochrome oxidase, both isopropylnoradrenaline and cold adaptation produced increases in these parameters. It appears that the isopropylnoradrenaline-treated animals mimic more closely the cold-adapted animals than do those with thyroxine treatment. However, the isopropylnoradrenaline-treated animals are not as resistant to cold as the cold-adapted animals.

scholarly journals RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

2012 ◽  
Vol 209 (13) ◽  
pp. 2409-2422 ◽  
Author(s):  
Heiyoun Jung ◽  
Benjamin Hsiung ◽  
Kathleen Pestal ◽  
Emily Procyk ◽  
David H. Raulet
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Stress Responses ◽  
Transcriptional Activation ◽  
Posttranscriptional Regulation ◽  
Cellular Proliferation ◽  
Control Cell ◽  
T Cell Subsets ◽  
Cell Cycle Entry

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.

scholarly journals NIK promotes metabolic adaptation of glioblastoma cells to bioenergetic stress

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Michael L. Kamradt ◽  
Ji-Ung Jung ◽  
Kathryn M. Pflug ◽  
Dong W. Lee ◽  
Victor Fanniel ◽  
...  
Keyword(s):  
Stress Responses ◽  
Glucose Deprivation ◽  
Metabolic Adaptation ◽  
Mitochondrial Morphology ◽  
Atp Production ◽  
Tumor Microenvironments ◽  
Iκb Kinase ◽  
Critical Measure

AbstractCancers, including glioblastoma multiforme (GBM), undergo coordinated reprogramming of metabolic pathways that control glycolysis and oxidative phosphorylation (OXPHOS) to promote tumor growth in diverse tumor microenvironments. Adaptation to limited nutrient availability in the microenvironment is associated with remodeling of mitochondrial morphology and bioenergetic capacity. We recently demonstrated that NF-κB-inducing kinase (NIK) regulates mitochondrial morphology to promote GBM cell invasion. Here, we show that NIK is recruited to the outer membrane of dividing mitochondria with the master fission regulator, Dynamin-related protein1 (DRP1). Moreover, glucose deprivation-mediated metabolic shift to OXPHOS increases fission and mitochondrial localization of both NIK and DRP1. NIK deficiency results in decreased mitochondrial respiration, ATP production, and spare respiratory capacity (SRC), a critical measure of mitochondrial fitness. Although IκB kinase α and β (IKKα/β) and NIK are required for OXPHOS in high glucose media, only NIK is required to increase SRC under glucose deprivation. Consistent with an IKK-independent role for NIK in regulating metabolism, we show that NIK phosphorylates DRP1-S616 in vitro and in vivo. Notably, a constitutively active DRP1-S616E mutant rescues oxidative metabolism, invasiveness, and tumorigenic potential in NIK−/− cells without inducing IKK. Thus, we establish that NIK is critical for bioenergetic stress responses to promote GBM cell pathogenesis independently of IKK. Our data suggest that targeting NIK may be used to exploit metabolic vulnerabilities and improve therapeutic strategies for GBM.

Sign in / Sign up

Export Citation Format

Share Document