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Tsubasa Furuhashi, Kazuichi Sakamoto
Autonomic nervous system (ANS) imbalances are involved in the etiology of cancer, allergy, and collagen diseases. Previously, we hypothesized that FoxO and HSF-1 limit autonomic stress responses via negative feedback on the ANS. Here, we evaluated the role of AKT, a negative regulator of FoxO, during activation of the ANS by loneliness stress in mice. Spontaneous motility was increased during loneliness stress and decreased after release from stress. The AKT activator SC79 attenuated stress-induced spontaneous motility, whereas the AKT inhibitor API-2 prevented decreases in motility after stress release...
October 18, 2016: Physiology & Behavior
Lorenza Brocca, Luana Toniolo, Carlo Reggiani, Roberto Bottinelli, Marco Sandri, Maria Antonietta Pellegrino
Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy program in the different disuse/inactivity conditions have not yet been completely dissected. It has been recently reported that inhibition of FoxO only partially spared muscle mass after denervation. The purposes of this study were: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model, (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation...
October 21, 2016: Journal of Physiology
Na Han, You Jeong Kim, Su Min Park, Seung Man Kim, Ji Suk Lee, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Mi-Kyung Kim, Byoung Doo Rhee, Jeong Hyun Park
BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear...
October 2016: Diabetes & Metabolism Journal
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
Nataly E Gruntenko, Natalya V Adonyeva, Elena V Burdina, Evgenia K Karpova, Olga V Andreenkova, Daniil V Gladkikh, Yury Y Ilinsky, Inga Yu Rauschenbach
The Forkhead BoxO transcription factor (FOXO) is a component of the insulin signalling pathway and plays a role in responding to adverse conditions, such as oxidative stress and starvation. In stressful conditions, FOXO moves from the cytosol to the nucleus where it activates gene expression programmes. Here, we show that FOXO in Drosophila melanogaster responds to heat stress as it does to other stressors. The catecholamine signalling pathway is another component of the stress response. In Drosophila, dopamine and octopamine levels rise steeply under heat, nutrition and mechanical stresses, which is followed by a decrease in the activity of synthesis enzymes...
October 17, 2016: Biology Open
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
Zdeněk Fryšák, David Karásek, Milan Halenka
Endocrine orbitopathy (EO) must be understood mainly as a result of oxidative stress. The pathological process finally affects both the appearance and vision of the patient. In the case of inappropriate or late treatment or lack of patient cooperation, it significantly influences the quality of life of those affected. In spite of the sophisticated dia-gnostic algorithms, in some cases it is difficult to confirm the diagnosis of EO. The range of laboratory methods, the essential part of the diagnostic process, has only recently been extended by the possibility of quantification of specific, stimulating immunoglobulins (TSI)...
2016: Vnitr̆ní Lékar̆ství
Xuejiao Liu, Yulong Chong, Yiming Tu, Ning Liu, Chenglong Yue, Zhenglei Qi, Huize Liu, Yao Yao, Hongmei Liu, Shangfeng Gao, Mingshan Niu, Rutong Yu
BACKGROUND: Malignant gliomas are associated with a high mortality rate, and effective treatment options are limited. Thus, the development of novel targeted treatments to battle this deadly disease is imperative. METHODS: In this study, we investigated the in vitro effects of the novel reversible chromosomal region maintenance 1 (CRM1) inhibitor S109 on cell proliferation in human gliomas. S109 was also evaluated in an intracranial glioblastoma xenograft model...
October 12, 2016: Journal of Hematology & Oncology
Ibanylla Kynjai Hynniewta Hadem, Ramesh Sharma
Time-dependent alterations in several biological processes of an organism may be characterized as aging. One of the effects of aging is the decline in cognitive functions. Dietary restriction (DR), an intervention where the consumption of food is lessened but without malnutrition, is a well-established mechanism that has a wide range of important outcomes including improved health span, delayed aging, and extension of lifespan of various species. It also plays a beneficial role in protecting against age-dependent deterioration of cognitive functions, and has neuroprotective properties against neurodegenerative diseases...
October 7, 2016: Cellular and Molecular Neurobiology
Parisa Kakanj, Bernard Moussian, Sebastian Grönke, Victor Bustos, Sabine A Eming, Linda Partridge, Maria Leptin
The TOR and Insulin/IGF signalling (IIS) network controls growth, metabolism and ageing. Although reducing TOR or insulin signalling can be beneficial for ageing, it can be detrimental for wound healing, but the reasons for this difference are unknown. Here we show that IIS is activated in the cells surrounding an epidermal wound in Drosophila melanogaster larvae, resulting in PI3K activation and redistribution of the transcription factor FOXO. Insulin and TOR signalling are independently necessary for normal wound healing, with FOXO and S6K as their respective effectors...
October 7, 2016: Nature Communications
Adi Pinkas, Michael Aschner
Advanced glycation end-products (AGEs) are non-enzymatically glycated proteins, lipids and nucleic acids. These compounds both originate exogenously and are formed endogenously, and are associated, along with one of their receptors - RAGE, with a variety of pathologies and neurodegeneration. Some of their deleterious effects include affecting insulin signaling and FOXO-related pathways in both receptor-dependent and -independent manner. A potential ameliorating agent for these effects is insulin, which is being studied in several in vivo and in vitro models; one of these models is C...
October 5, 2016: Chemical Research in Toxicology
Yiliang Wei, Rewatee H Gokhale, Anne Sonnenschein, Kelly Mone't Montgomery, Andrew Ingersoll, David N Arnosti
Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated...
October 1, 2016: Development
Yutaka Kurebayashi, Yukiko Baba, Akiko Minowa, Niken Adiba Nadya, Miyuki Azuma, Akihiko Yoshimura, Shigeo Koyasu, Shigenori Nagai
Transforming growth factor-β (TGF-β) is a pivotal cytokine in the differentiation of regulatory T cells, and Foxo transcription factors positively regulate this process. On the other hand, the function of Foxo transcription factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF-β in many types of cells; yet the role of TGF-β in Akt activity and its downstream substrates in CD4(+) T cells, including Foxo transcription factors, remains to be determined. Herein, we demonstrate that TGF-β selectively induces Akt phosphorylation at Ser473 but not at Thr308 in a class IA PI3K-dependent manner in CD4(+) T cells, resulting in the phosphorylation and inhibition of Foxo transcription factors and negatively regulating the differentiation of induced regulatory T cells (iTregs)...
October 1, 2016: Biochemical and Biophysical Research Communications
Andriy Stelmakh, Orest Abrahamovych, Andriy Cherkas
Highly purified calf hemodialysate (HPCH) known as Actovegin® or Solcoseryl® is one of the most controversial drugs currently marketed worldwide. It is not registered as drug in some countries and therefore its medical use there is illegal, while in others it is often among the top 10 of the best-selling medications. It could be also found in the list of the "most useless drugs" and was banned for short time by World Anti-Doping Agency as performance enhancer. However, the degree of its usefulness or uselessness remains unclear and there is not enough convincing data to make reliable conclusions...
October 2016: Medical Hypotheses
Deying Yang, Ting Lian, Jianbo Tu, Uma Gaur, Xueping Mao, Xiaolan Fan, Diyan Li, Ying Li, Mingyao Yang
Dietary restriction (DR) extends lifespan in many species which is a well-known phenomenon. Long non-coding RNAs (lncRNAs) play an important role in regulation of cell senescence and important age-related signaling pathways. Here, we profiled the lncRNA and mRNA transcriptome of fruit flies at 7 day and 42 day during DR and fully-fed conditions, respectively. In general, 102 differentially expressed lncRNAs and 1406 differentially expressed coding genes were identified. Most informatively we found a large number of differentially expressed lncRNAs and their targets enriched in GO and KEGG analysis...
September 27, 2016: Aging
Matthias Dottermusch, Theresa Lakner, Tobias Peyman, Marinella Klein, Gerd Walz, Elke Neumann-Haefelin
Recent studies have revealed a variety of genes and mechanisms that influence the rate of aging progression. In this study, we identified cell cycle factors as potent regulators of health and longevity in C. elegans. Focusing on the cyclin-dependent kinase 2 (cdk-2) and cyclin E (cye-1), we show that inhibition of cell cycle genes leads to tolerance towards environmental stress and longevity. The reproductive system is known as a key regulator of longevity in C. elegans. We uncovered the gonad as the central organ mediating the effects of cell cycle inhibition on lifespan...
September 25, 2016: Aging
Reza Yazdani, Mazdak Ganjalikhani-Hakemi, Mohammad Esmaeili, Hassan Abolhassani, Shahram Vaeli, Abbas Rezaei, Zohre Sharifi, Gholamreza Azizi, Nima Rezaei, Asghar Aghamohammadi
Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency characterized by recurrent infectious. We evaluated whether defective PI3K/Akt/FoxO pathway could influence B-cell fate. Determination of B-cell subsets in CVD patients and healthy donors (HDs) were performed using flow cytometry. We evaluated mRNA level and protein expression of PI3K, Akt and FoxO molecules using real-time PCR and flow cytometry, respectively. Moreover, phosphorylated Akt (p-Akt) expression in B-cells has also been measured by flowcytometry...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Purnima Gupta, Supriya Srivastav, Shriya Saha, Pijush K Das, Anindita Ukil
In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival...
November 1, 2016: Cell Death and Differentiation
Gang Li, Qing-Shan Li, Wen-Bin Li, Jian Wei, Wen-Kai Chang, Zhi Chen, Hu-Yun Qiao, Ying-Wei Jia, Jiang-Hua Tian, Bing-Sheng Liang
Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle) and a typical fast muscle (tibialis anterior muscle) at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles...
August 2016: Neural Regeneration Research
Ju Zhang, Ruona Shi, Haifeng Li, Yanxia Xiang, Lingyun Xiao, Minghua Hu, Fangli Ma, Chung Wah Ma, Zebo Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. MATERIALS AND METHODS: The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C...
November 4, 2016: Journal of Ethnopharmacology
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