scholarly journals Mechanism underlying starvation-dependent modulation of olfactory behavior in Drosophila larva

2019 ◽  
Author(s):  
Eryn Slankster ◽  
Sai Kollala ◽  
Dominique Baria ◽  
Brianna Dailey-Krempel ◽  
Roshni Jain ◽  
...  

ABSTRACTStarvation enhances olfactory sensitivity that encourage animals to search for food. The molecular mechanisms that enable sensory neurons to remain flexible and adapt to a particular internal state remain poorly understood. Here, we study the roles of GABA and insulin signaling in starvation-dependent modulation of olfactory sensory neuron (OSN) function in the Drosophila larva. We show that GABAB-receptor and insulin-receptor are necessary for OSN modulation. Using a novel OSN-specific gene expression analysis, we explore downstream targets of insulin signaling in OSNs. Our results strongly suggest that insulin and GABA signaling pathways interact within OSNs and modulate OSN function by impacting olfactory information processing and neurotransmission. We further show that manipulating these signaling pathways specifically in the OSNs impact larval feeding behavior and its body weight. These results challenge the prevailing model of OSN modulation and highlight opportunities to better understand OSN modulation mechanisms and their relationship to animal physiology.

2011 ◽  
Vol 1 (2) ◽  
pp. 52-61
Author(s):  
Bernardo Neme Ide ◽  
Fernanda Lorenzi Lazarim ◽  
Denise Vaz de Macedo

A resposta adaptativa ao treinamento físico é determinada pelo tipo, volume e frequência de aplicação dos estímulos, que ativam vias de sinalização distintas, a transcrição de genes específicos e posterior síntese protéica. O treinamento resistido está relacionado à ativação da enzima mTOR, proporcionada pelo hormônio IGF-1 e estimulada pela insulina, quando um carboidrato é consumido após a atividade física. Estas vias de sinalização levam à inibição da transcrição de genes relacionados à atrofia e aumento da síntese de proteínas contráteis e metabólicas, proporcionando um aumento da massa muscular, conhecido como hipertrofia. Atualmente, evidências sugerem que, além das sinalizações dos hormônios, os estímulos mecânicos (mecanotransdução) também podem influenciar a ativação gênica durante o processo hipertrófico. A ativação de células satélites, proporcionada pelo estresse mecânico, fatores de crescimento, radicais livres e citocinas é de suma importância para o crescimento muscular. Devido à relevância deste assunto, o presente trabalho traz uma revisão da literatura a respeito dos processos envolvidos na resposta hipertrófica, em decorrência do treinamento físico. Embora o processo hipertrófico seja bastante estudado, os mecanismos moleculares, tanto em nível gênico quanto protéico, envolvidos no processo adaptativo ainda não são totalmente compreendidos. Neste sentido, o avanço nas técnicas de biologia molecular como genômica, transcriptoma e proteômica abrem caminhos para futuras investigações nesta área.Palavras-chave: treino resistido, adaptações ao treinamento de força, células satélites, IGF-1, síntese protéica.The adaptation process to physical training is determined by the type, volume and frequency of stimulation, activating distinct signaling pathways, specific gene transcription and then protein synthesis. Resistance-training is related to mTOR enzyme activation induced by IGF-1 and stimulated by insulin when carbohydrates are consumed after physical activity. These pathways, may lead to the inhibition of gene transcription related to atrophy and the increment of contractile and metabolic protein synthesis causing an increase on muscle mass known as hypertrophy. Presently, there is evidence to suggest that besides hormone signaling pathways, mechanical stimulation (mechanotransduction) may also influence the gene activation during the hypertrophic process. The satellite cells activation induced by mechanical stress, growth factors, free radicals, and cytokines is crucial for muscle growth. Due to the importance of this topic, the present study, proposes a literature review about the processes related to the hypertrophic responses to physical training. Despite the frequent studies on the hypertrophic process, the molecular mechanisms (both at gene and protein levels) involved in the adaptation process is yet to be fully understood. Thus, advances in molecular biology techniques such as genomic, transcriptoma and proteomic open ways for future investigations in this area.Key words: Resistance-training, strength training adaptations, satellite cells, IGF-1, protein synthesis.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Jung Heo ◽  
Sung-E Choi ◽  
Ja Young Jeon ◽  
Seung Jin Han ◽  
Dae Jung Kim ◽  
...  

Background. It has been suggested that visfatin, which is an adipocytokine, exhibits proinflammatory properties and is associated with insulin resistance. Insulin resistance and inflammation are the principal pathogeneses of nonalcoholic fatty liver disease (NAFLD), but the relationship, if any, between visfatin and NAFLD remains unclear. Here, we evaluated the effects of visfatin on hepatic inflammation and insulin resistance in HepG2 cells and examined the molecular mechanisms involved. Methods. After treatment with visfatin, the inflammatory cytokines IL-6, TNF-α, and IL-1β were assessed by real-time polymerase chain reaction (RT-PCR) and immunocytochemical staining in HepG2 cells. To investigate the effects of visfatin on insulin resistance, we evaluated insulin-signaling pathways, such as IR, IRS-1, GSK, and AKT using immunoblotting. We assessed the intracellular signaling molecules including STAT3, NF-κB, IKK, p38, JNK, and ERK by western blotting. We treated HepG2 cells with both visfatin and either AG490 (a JAK2 inhibitor) or Bay 7082 (an NF-κB inhibitor); we examined proinflammatory cytokine mRNA levels using RT-PCR and insulin signaling using western blotting. Results. In HepG2 cells, visfatin significantly increased the levels of proinflammatory cytokines, reduced the levels of proteins (e.g., phospho-IR, phospho-IRS-1 (Tyr612), phospho-AKT, and phospho-GSK-3α/β) involved in insulin signaling, and increased IRS-1 S307 phosphorylation compared to controls. Interestingly, visfatin increased the activities of the JAK2/STAT3 and IKK/NF-κB signaling pathways but not those of the JNK, p38, and ERK pathways. Visfatin-induced inflammation and insulin resistance were regulated by JAK2/STAT3 and IKK/NF-κB signaling; together with AG490 or Bay 7082, visfatin significantly reduced mRNA levels of IL-6, TNF-α and IL-1β and rescued insulin signaling. Conclusion. Visfatin induced proinflammatory cytokine production and inhibited insulin signaling via the STAT3 and NF-κB pathways in HepG2 cells.


2002 ◽  
Vol 283 (5) ◽  
pp. E1084-E1101 ◽  
Author(s):  
Ahmad R. Sedaghat ◽  
Arthur Sherman ◽  
Michael J. Quon

We develop a mathematical model that explicitly represents many of the known signaling components mediating translocation of the insulin-responsive glucose transporter GLUT4 to gain insight into the complexities of metabolic insulin signaling pathways. A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate-1, activation of phosphatidylinositol 3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C-ζ is coupled with previously validated subsystem models of insulin receptor binding, receptor recycling, and GLUT4 translocation. A system of differential equations is defined by the structure of the model. Rate constants and model parameters are constrained by published experimental data. Model simulations of insulin dose-response experiments agree with published experimental data and also generate expected qualitative behaviors such as sequential signal amplification and increased sensitivity of downstream components. We examined the consequences of incorporating feedback pathways as well as representing pathological conditions, such as increased levels of protein tyrosine phosphatases, to illustrate the utility of our model for exploring molecular mechanisms. We conclude that mathematical modeling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signaling.


2009 ◽  
Vol 297 (3) ◽  
pp. E568-E577 ◽  
Author(s):  
Maria Assunta Potenza ◽  
Francesco Addabbo ◽  
Monica Montagnani

Hemodynamic actions of insulin depend largely on the hormone's ability to stimulate synthesis and release of endothelial mediators, whose balanced activity ensures dynamic control of vascular function. Nitric oxide (NO), endothelin-1 (ET-1), and reactive oxygen species (ROS) are important examples of endothelial mediators with opposing properties on vascular tone, hemostatic processes, and vascular permeability. Reduced NO bioavailability, resulting from either insufficient production or increased degradation of NO, characterizes endothelial dysfunction. In turn, endothelial dysfunction predicts vascular complications of metabolic and hemodynamic disorders. In the cardiovascular system, insulin stimulates the production and release of NO, ET-1, and ROS via activation of distinct intracellular signaling pathways. Under insulin-resistant conditions, increased insulin concentrations and/or impaired insulin-signaling pathways in the vasculature may contribute to imbalance in secretion of endothelial mediators that promote pathogenesis of vascular abnormalities. This short review describes signaling pathways involved in insulin-stimulated release of NO, ROS, and ET-1 and suggests possible molecular mechanisms by which abnormal insulin signaling may contribute to endothelial dysfunction.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Luca Fagnocchi ◽  
Stefania Mazzoleni ◽  
Alessio Zippo

Stem cells balance their self-renewal and differentiation potential by integrating environmental signals with the transcriptional regulatory network. The maintenance of cell identity and/or cell lineage commitment relies on the interplay of multiple factors including signaling pathways, transcription factors, and the epigenetic machinery. These regulatory modules are strongly interconnected and they influence the pattern of gene expression of stem cells, thus guiding their cellular fate. Embryonic stem cells (ESCs) represent an invaluable tool to study this interplay, being able to indefinitely self-renew and to differentiate towards all three embryonic germ layers in response to developmental cues. In this review, we highlight those mechanisms of signaling to chromatin, which regulate chromatin modifying enzymes, histone modifications, and nucleosome occupancy. In addition, we report the molecular mechanisms through which signaling pathways affect both the epigenetic and the transcriptional state of ESCs, thereby influencing their cell identity. We propose that the dynamic nature of oscillating signaling and the different regulatory network topologies through which those signals are encoded determine specific gene expression programs, leading to the fluctuation of ESCs among multiple pluripotent states or to the establishment of the necessary conditions to exit pluripotency.


Diabetes ◽  
1998 ◽  
Vol 47 (2) ◽  
pp. 179-185 ◽  
Author(s):  
R. W. Stevenson ◽  
D. K. Kreutter ◽  
K. M. Andrews ◽  
P. E. Genereux ◽  
E. M. Gibbs

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.


2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.


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