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AMP activated kinase

Ying Yang, Hui Fang, Gang Xu, Yanfeng Zhen, Yazhong Zhang, Jinli Tian, Dandan Zhang, Guyue Zhang, Jing Xu
Liraglutide is a type of glucagon‑like‑peptide 1 receptor agonist, which has been reported as a novel type of antidiabetic agent with numerous benefits, including cardiovascular and neuroprotective effects. To the best of our knowledge, few studies to date have reported the potential mechanism underlying the neuroprotective effects of liraglutide on rats with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the neuroprotective actions of liraglutide in diabetic rats and to determine the mechanisms underlying these effects...
June 18, 2018: Molecular Medicine Reports
Si-Yoon Han, Yun-Jeong Jeong, Yongsoo Choi, Soon-Kyung Hwang, Young-Seuk Bae, Young-Chae Chang
Mitochondria are well known for their important roles in oxidative phosphorylation, amino acid metabolism, fatty acid oxidation and ion homeostasis. Although the effects of mitochondrial dysfunction on tumorigenesis in various cancer cells have been reported, the correlation between mitochondrial dysfunction and epithelial‑to‑mesenchymal transition (EMT) in lung cancer development and metastasis has not been well elucidated. In the present study, the effects of mitochondrial dysfunction on EMT and migration in lung cancer cells were investigated using inhibitors of mitochondrial respiration, oligomycin A and antimycin A...
June 18, 2018: International Journal of Molecular Medicine
Rishi Raj Chhipa, Qiang Fan, Jane Anderson, Ranjithmenon Muraleedharan, Yan Huang, Georgianne Ciraolo, Xiaoting Chen, Ronald Waclaw, Lionel M Chow, Zaza Khuchua, Matthew Kofron, Matthew T Weirauch, Ady Kendler, Christopher McPherson, Nancy Ratner, Ichiro Nakano, Nupur Dasgupta, Kakajan Komurov, Biplab Dasgupta
Stress is integral to tumour evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activates the bioenergetic sensor AMP kinase (AMPK) and, to survive, tumour cells hijack an AMPK-regulated stress response pathway conserved in normal cells. Analysis of The Cancer Genome Atlas data revealed that AMPK isoforms are highly expressed in the lethal human cancer glioblastoma (GBM). We show that AMPK inhibition reduces viability of patient-derived GBM stem cells (GSCs) and tumours...
June 18, 2018: Nature Cell Biology
Ismael González-García, Pablo Blanco, Ánxela Estévez-Salguero, Cristina Contreras, Amparo Romero-Picó, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, Manuel Tena-Sempere, Sulay Tovar, Miguel López
Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that, ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism...
June 18, 2018: Journal of Endocrinology
Tsong-Min Chang, Ting-Ya Yang, Yu-Lin Niu, Huey-Chun Huang
Dictamni dasycarpus is a type of Chinese medicine made from the root bark of D. dasycarpus . It has been reported to show a wide spectrum of biological and pharmacological effects, for example, it has been used widely for the treatment of rheumatism, nettle rash, itching, jaundice, chronic hepatitis and skin diseases. In the current study, D. dasycarpus extract was investigated for its antioxidant and anti-inflammatory effects, as well as its capability to alleviate oxazolone-induced skin damage in mice. The possible anti-inflammatory mechanism of D...
June 15, 2018: Antioxidants (Basel, Switzerland)
Soonwoong Jung, Hyeonwi Son, Chung Eun Hwang, Kye Man Cho, Sang Won Park, Hyun Joon Kim
Non-alcoholic steatosis is a common health problem worldwide due to altered food habits and life styles, and it is intimately linked with various metabolic disorders. In the present study, we investigated the molecular mechanism of Ganoderma lucidum (GL) against the development of non-alcoholic steatosis using in vivo and in vitro settings. C57BL/6 mice fed with normal diet (ND) or high fat diet (HFD) were administered GL extract or vehicle for 16 weeks. HFD feeding increased serum alanine aminotransferase level and hepatic lipid droplet, but these increases were significantly attenuated by GL...
June 15, 2018: Journal of Clinical Medicine
Aekkacha Moonwiriyakit, Panisara Wattanaphichet, Varanuj Chatsudthipong, Chatchai Muanprasat
Tight junctions play key roles in the regulation of airway epithelial barrier function and promotion of tight junction integrity is beneficial to lung health. G-protein coupled receptor (GPR) 40 has been identified as a receptor of polyunsaturated fatty acids. This study aimed to investigate the function of GPR40 in regulating tight junction assembly in human airway epithelial cells (Calu-3 cells) using GW9508, a GPR40 agonist. Immunoblotting and immunofluorescence analyses showed that Calu-3 cells expressed both types of polyunsaturated fatty acid receptors including GPR40 and GPR120...
June 18, 2018: Tissue Barriers
Joshua T Atkinson, Alicia M Jones, Quan Zhou, Jonathan J Silberg
Deep mutational scanning has been used to create high-resolution DNA sequence maps that illustrate the functional consequences of large numbers of point mutations. However, this approach has not yet been applied to libraries of genes created by random circular permutation, an engineering strategy that is used to create open reading frames that express proteins with altered contact order. We describe a new method, termed circular permutation profiling with DNA sequencing (CPP-seq), which combines a one-step transposon mutagenesis protocol for creating libraries with a functional selection, deep sequencing and computational analysis to obtain unbiased insight into a protein's tolerance to circular permutation...
April 18, 2018: Nucleic Acids Research
Su-Juan Pei, Huai-Yuan Zhu, Jin-Hui Guo, Xin Zhang, Zhi-Jian Deng
Obesity and diabetes are associated with diabetic cardiomyopathy (DCM). However, the pathogenesis of DCM is not fully understood. Cannabinoid receptor gene (CNR1) has been a drug target for the treatment of obesity. Here, we reported that CNR1 expression was increased in high fat diet (HFD)-induced heart of mice. Following, the wild type (CNR1+/+ ) and CNR1-knockout (CNR1-/- ) mice were employed and subjected to HFD treatments for 16 weeks to further investigate the effects of CNR1 on DCM. The results indicated that CNR1 knockout mice after HFD feeding exhibited a significant decrease of body weight and lipid accumulation in serum...
June 14, 2018: Biochemical and Biophysical Research Communications
Kalahe Hewage Iresha Nadeeka Madushani Herath, Jinhee Cho, Areum Kim, Tae Kil Eom, Ju-Sung Kim, Jae-Bum Kim, Yang Hoi Doh, Youngheun Jee
ETHNOPHARMACOLOGICAL RELEVANCE: Sasa quelpaertensis Nakai is an edible dwarf bamboo cultivated mainly in Jeju Island, South Korea and its leaf displays various health-promoting properties including antioxidant scavenging. AIM OF THE STUDY: In this study, we aimed at elucidating its hepatoprotective effect against alcohol-induced fatty liver. METHODS: In in vitro study, we evaluated the cytotoxicity and hepatoprotective effect of different solvent fractions (aqua, butanol, chloroform, ethyl acetate and hexane) of 80% EtOH extract of S...
June 12, 2018: Journal of Ethnopharmacology
Ayumu Takeno, Ippei Kanazawa, Masakazu Notsu, Ken-Ichiro Tanaka, Toshitsugu Sugimoto
Phloretin, a glucose transporter (GLUT) inhibitor, has pleiotropic effects. The present study examined the effects of phloretin on the commitment of marrow stromal cells to adipocytes, using the mouse marrow stromal cell line ST2. Oil red O staining showed that treatment with phloretin 10⁻100 µM promoted lipid accumulation. Real-time PCR showed that phloretin significantly increased the expression of adipogenic markers, including PPARγ, C/EBPα, fatty acid synthase, fatty acid-binding protein 4, and adiponectin...
June 14, 2018: International Journal of Molecular Sciences
Yanwei Li, Qian Gong, Wenjin Guo, Xingchi Kan, Dianwen Xu, He Ma, Shoupeng Fu, Juxiong Liu
Farrerol has been proved to have an anti-inflammatory effect. However, the effects of farrerol on mastitis have not been investigated. This study was aimed to investigate the effect and mechanism of farrerol in lipopolysaccharide (LPS)-induced mouse mastitis and LPS-induced inflammatory response of mouse mammary epithelial cells (mMECs). In vivo, LPS were injected to the tetrad pair of nipples for establishing mouse mastitis, and then tested the effect of farrerol on histopathological changes, inflammatory response and activation degree of protein kinase B (AKT), nuclear factor-kappa B p65 (NF-κB p65), p38, extracellular regulated protein kinase (ERK1/2)...
June 14, 2018: International Journal of Molecular Sciences
Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart
Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors...
June 14, 2018: Cancers
Alicia M Salvi, Kris A DeMali
Throughout their lifetimes, all cells experience force. These forces are sensed by cell surface adhesion receptors, such as the cadherins and integrins. Much attention has focused on identifying how these adhesion receptors transmit force. In contrast, less is known regarding how these force-activated pathways are integrated with other cellular processes. In this review, we describe how cadherins and integrins transmit force, and discuss how these adhesion receptors are linked to cell metabolism. We focus on understanding this connection by highlighting how the cadherins and integrins interact with a master regulator of energy homeostasis, AMP-activated protein kinase (AMPK) and its upstream activator, Liver Kinase B1 (LKB1)...
June 11, 2018: Current Opinion in Cell Biology
Yapeng Li, Dianhong Zhang, Lingyao Kong, Huiting Shi, Xinyu Tian, Lu Gao, Yuzhou Liu, Leiming Wu, Binbin Du, Zhen Huang, Cui Liang, Zheng Wang, Rui Yao, Yanzhou Zhang
Metabolic dysfunction is a hallmark of cardiac hypertrophy and heart failure. During cardiac failure, the metabolism of cardiomyocyte switches from fatty acid oxidation to glycolysis. However, the roles of key metabolic enzymes in cardiac hypertrophy are not understood fully. Here in the present work, we identified Aldolase A (AldoA) as a core regulator of cardiac hypertrophy. The mRNA and protein levels of AldoA were significantly up-regulated in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced hypertrophic mouse hearts...
June 11, 2018: Experimental Cell Research
In-Ja Park, Quynh Hoa Tran, Ain Syafiza Mohd Amin, Thanh Lan Chu, Goowon Yang, Wonchae Choe, Insug Kang, Sung Soo Kim, Joohun Ha
AMP-activated protein kinase (AMPK) functions as a cellular energy sensor by monitoring the cellular AMP:ATP ratio and plays a central role in cellular and whole-body energy homeostasis. Recent studies have suggested that AMPK also contribute to cell cycle regulation, but its role in this field remains almost elusive. In the present study, we report that AMPKα1 was transiently activated during G1 /S transition phase in NIH3T3 cells in the absence of any metabolic stress. Inhibition of AMPK activity at G1 /S transition phase completely blocked cells from entering S phase; in contrast, persistent activation of AMPK at G1 /S transition phase allowed cells to normally enter S phase, but these cells failed to proceed to G2 /M phase, stacking at S phase...
June 11, 2018: Biochemical and Biophysical Research Communications
J Uerlings, Z G Song, X Y Hu, S K Wang, H Lin, Johan Buyse, N Everaert
Dysfunction of the intestinal epithelial barrier under elevated temperatures is assumed to prompt pathological conditions and to eventually impede chickens' growth, resulting in massive economic losses in broiler industries. The aims of this research were to determine the impact of acute heat stress on the intestinal tight junction network of broiler chicks (Gallus domesticus L.) and to elucidate whether adenosine monophosphate-activated protein kinase (AMPK) was involved in the integrated response of the broiler's gastrointestinal tract to heat stress...
June 13, 2018: Poultry Science
Yujie Liu, An Song, Xi Yang, Yunfeng Zhen, Weiwei Chen, Linquan Yang, Chao Wang, Huijuan Ma
The development of type‑2 diabetes and its complications is associated with lipid metabolism disorder. Farnesoid X receptor (FXR) has an important role in regulating lipid and glucose metabolism. However, the underlying mechanism of this remains unclear. The present study investigated the role of fexaramine (Fex), an FXR agonist, on lipid metabolism. For this purpose, 6‑week‑old db/db mice were treated with Fex for 8 weeks via oral gavage and db/db mice treated with corn oil were used as controls. Body weight and food intake were monitored daily and bi‑weekly, respectively...
June 5, 2018: International Journal of Molecular Medicine
Guo-Sheng Xiao, Yan-Hui Zhang, Yan Wang, Hai-Ying Sun, Clive M Baumgarten, Gui-Rong Li
BACKGROUND AND PURPOSE: Adrenergic regulation of cell volume-regulated chloride current (ICl.vol ) is species-dependent. The present study investigates the mechanism underlying adrenergic regulation of ICl.vol in human atrial myocytes. EXPERIMENTAL APPROACH: A conventional whole-cell patch voltage-clamp technique was utilized to record membrane current in human atrial myocytes. ICl.vol was evoked by hyposmotic bath solution (0.6-times isosmotic, 0.6T). KEY RESULTS: ICl...
June 13, 2018: British Journal of Pharmacology
Lucy C Fox, Costas K Yannakou, Georgina Ryland, Stephen Lade, Michael Dickinson, Belinda A Campbell, Henry Miles Prince
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p...
June 13, 2018: International Journal of Molecular Sciences
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