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AMP-activated protein kinase

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https://www.readbyqxmd.com/read/29235249/anticancer-effects-of-resveratrol-in-canine-hemangiosarcoma-cell-lines
#1
A Carlson, K S Alderete, M K O Grant, D M Seelig, L C Sharkey, B N M Zordoky
Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti-proliferative and/or pro-apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs...
December 13, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29234282/effect-of-methanolic-extract-of-dandelion-roots-on-cancer-cell-lines-and-amp-activated-protein-kinase-pathway
#2
Gauhar Rehman, Muhammad Hamayun, Amjad Iqbal, Sumera Afzal Khan, Hamayoon Khan, Adeeb Shehzad, Abdul Latif Khan, Anwar Hussain, Ho-Youn Kim, Jamshaid Ahmad, Ayaz Ahmad, Abid Ali, In-Jung Lee
Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29233869/mtorc1-as-the-main-gateway-to-autophagy
#3
REVIEW
Yoana Rabanal-Ruiz, Elsje G Otten, Viktor I Korolchuk
Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29230603/amp-activated-protein-kinase-activation-in-mediating-phenylalanine-induced-neurotoxicity-in-experimental-models-of-phenylketonuria
#4
Lihua Lu, Xiaoming Ben, Lingling Xiao, Min Peng, Yongjun Zhang
Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated...
December 11, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29230216/metabolism-controls-the-balance-of-th17-t-regulatory-cells
#5
REVIEW
Licheng Sun, Jinrong Fu, Yufeng Zhou
Accumulating evidence indicates that metabolism reprogramming is critically important to T cell differentiation, and manipulating metabolic pathways in T cells can shape their fate and function. During T cell differentiation, metabolism provides T cells with energy as well as precursors for various biological processes. Some key metabolic reactions, such as glycolysis, oxidative phosphorylation and fatty acid oxidation, are also considered to play important roles in T cell activation and differentiation. In this review, we will explain why cellular metabolism is important for the Th17/T-regulatory (Treg) cell balance and how metabolism reprogramming impacts this balance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29229994/autophagy-induced-during-apoptosis-degrades-mitochondria-and-inhibits-type-i-interferon-secretion
#6
Lisa M Lindqvist, Daniel Frank, Kate McArthur, Toby A Dite, Michael Lazarou, Jonathan S Oakhill, Benjamin T Kile, David L Vaux
Cells undergoing Bax/Bak-mediated apoptosis exhibit signs of autophagy, but how it is activated and its significance is unknown. By directly activating Bax/Bak with BH3-only proteins or BH3 mimetic compounds, we demonstrate that mitochondrial damage correlated with a rapid increase in intracellular [AMP]/[ATP], phosphorylation of 5' AMP-activated protein kinase (AMPK), and activation of unc-51 like autophagy activating kinase 1 (ULK1). Consequently, autophagic flux was triggered early in the apoptotic pathway, as activation of the apoptosome and caspases were not necessary for its induction...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229115/cell-specific-regulation-of-inos-by-amp-activated-protein-kinase-in-primary-rat-hepatocytes
#7
Baochun Zhang, Jaganathan Lakshmanan, Yibo Du, Jason W Smith, Brian G Harbrecht
BACKGROUND: AMP-activated protein kinase (AMPK) regulates several metabolic pathways in hepatocytes that are critical to the hepatic response to sepsis and shock. Induction of nitric oxide synthesis is an important response to sepsis, inflammation and shock and many of the stimuli that upregulate inducible nitric oxide synthase (iNOS) also activate AMPK. AMPK inhibits nitric oxide (NO) production in skeletal and cardiac muscle cells, but the role of AMPK in regulating iNOS expression in hepatocytes has not been determined...
January 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29228674/the-regulatory-role-of-aberrant-phosphatase-and-tensin-homologue-and-liver-kinase-b1-on-akt-mtor-c-myc-axis-in-pancreatic-neuroendocrine-tumors
#8
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
Pancreatic neuroendocrine tumor (pNET) is an uncommon type of pancreatic neoplasm. Low Phosphatase and Tensin Homologue (PTEN) expression and activation of the mechanistic target of rapamycin (mTOR) pathway have been noted in pNETs, and the former is associated with poor survival in pNET patients. Based on the results of the RADIANT-3 study, everolimus, an oral mTOR inhibitor, has been approved to treat advanced pNETs. However, the exact regulatory mechanism for the mTOR pathway in pNETs remains largely unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224101/estradiol-regulation-of-brown-adipose-tissue-thermogenesis
#9
Ismael González-García, Manuel Tena-Sempere, Miguel López
Physiologically, estrogens carry out a myriad of functions, the most essential being the regulation of the reproductive axis. Currently, it is also dogmatic that estrogens play an important role modulating energy balance and metabolism. In this sense, it is well known that low estrogens levels, occurring due to ovarian insufficiency, in conditions such as menopause or ovariectomy (OVX), are associated with increased food intake and decreased energy expenditure, leading to weight gain and obesity at long term...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29219657/the-levels-of-mutant-k-ras-and-mutant-n-ras-are-rapidly-reduced-in-a-beclin1-atg5-dependent-fashion-by-the-irreversible-erbb1-2-4-inhibitor-neratinib
#10
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Cindy Sander, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29214644/acute-oxygen-sensing-by-the-carotid-body-a-rattlebag-of-molecular-mechanisms
#11
Ryan J Rakoczy, Christopher N Wyatt
The molecular underpinnings of the oxygen-sensitivity of the carotid body Type I cells are becoming better defined as research begins to identify potential interactions between previously separate theories. Nevertheless, the field of oxygen-chemoreception still presents the general observer with a bewildering array of potential signalling pathways by which a fall in oxygen levels might initiate Type I cell activation. The purpose of this brief review is to address five of the current oxygen-sensing hypotheses...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29213353/resveratrol-prevents-ros-induced-apoptosis-in-high-glucose-treated-retinal-capillary-endothelial-cells-via-the-activation-of-ampk-sirt1-pgc-1%C3%AE-pathway
#12
Jun Li, Songping Yu, Jia Ying, Tianyan Shi, Peipei Wang
Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy. However, the mechanism(s) underlying this protective effect has not been fully elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro model, were used to investigate the mechanism of RSV. Our results showed that high glucose induced significant cellular apoptosis in BRECs, which was accompanied by increased intracellular levels of reactive oxygen species (ROS) and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both inhibited by RSV...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29212931/suppression-of-zika-virus-infection-and-replication-in-endothelial-cells-and-astrocytes-by-pka-inhibitor-pki-14-22
#13
Fan Cheng, Suzane Ramos da Silva, I-Chueh Huang, Jae U Jung, Shou-Jiang Gao
The recent outbreak of Zika virus (ZIKV), a re-emerging flavivirus, and its associated neurological disorders, such as Guillain-Barré (GB) syndrome and microcephaly, have generated an urgent need for developing effective ZIKV vaccines and therapeutic agents. Here, we used human endothelial cells and astrocytes, both of which represent key cell types for ZIKV infection, to identify potential inhibitors for ZIKV replication. Because several pathways, including AMP-activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling pathways, have been reported to play important roles in flavivirus replication, we tested inhibitors or agonists of these pathways for their effects on ZIKV replication...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212261/cordycepin-stimulates-autophagy-in-macrophages-and-prevents-atherosclerotic-plaque-formation-in-apoe-mice
#14
Xin Li, Yue Zhou, Xue Zhang, Xiaoxue Cao, Chongming Wu, Peng Guo
Autophagy in macrophages plays a key role in the pathogenesis and progression of atherosclerosis and has become a potential therapeutic target. Here we show that cordycepin (Cpn), a natural derivative of adenosine, markedly reduced atherosclerotic plaque and ameliorated associated symptoms such as dyslipidemia, hyperglycemia and inflammation in ApoE-/- mice. Supplementation of Cpn dose-dependently inhibited oxLDL-elicited foam cell formation and modulated intracellular cholesterol homeostasis by inhibiting cholesterol uptake and promoting cholesterol efflux in RAW264...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#15
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#16
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#17
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...
December 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29207101/diosgenin-prevents-high-fat-diet-induced-rat-non-alcoholic-fatty-liver-disease-through-the-ampk-and-lxr-signaling-pathways
#18
Silu Cheng, Shufang Liang, Qun Liu, Zhengting Deng, Yuanhui Zhang, Juan Du, Ya'ni Zhang, Shu Li, Binbin Cheng, Changquan Ling
Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207028/role-of-the-cofilin-2-gene-in-regulating-the-myosin-heavy-chain-genes-in-mouse-myoblast-c2c12-cells
#19
Hongyan Zhu, Huixin Yang, Song Zhao, Junfeng Zhang, Dan Liu, Yumin Tian, Zhiyi Shen, Yuhong Su
The cofilin 2 (CFL2) and myosin heavy chain (MyHC) genes play a key role in muscle development and myofibrillar formation. The aim of the present study was to investigate the effect of CFL2 on genes involved in fiber formation and the mechanisms underlying this process. Undifferentiated and differentiated C2C12 cells (UDT and DT, respectively) were transfected with CFL2 small interfering RNA (siRNA). CFL2 mRNA and protein levels were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blotting, respectively...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207025/anti-obesity-effects-of-pectinase-and-cellulase-enzyme%C3%A2-treated-ecklonia%C3%A2-cava-extract-in-high%C3%A2-fat-diet%C3%A2-fed-c57bl-6n-mice
#20
In-Hye Kim, Jung-Wook Choi, Min-Kyeong Lee, Chang-Ju Kwon, Taek-Jeong Nam
The present study investigated the anti‑obesity effects of enzyme‑treated Ecklonia cava extract (EEc) in C57BL/6N mice with high‑fat diet (HFD)‑induced obesity. The EEc was separated and purified with the digestive enzymes pectinase (Rapidase X‑Press L) and cellulase (Rohament CL) and its effects on the progression of HFD‑induced obesity were examined over 10 weeks. The mice were divided into 6 groups (n=10/group) as follows: Normal diet group, HFD group, mice fed a HFD with 25 mg/kg/day Garcinia cambogia extract and mice fed a HFD with 5, 25 or 150 mg/kg/day EEc (EHD groups)...
November 28, 2017: International Journal of Molecular Medicine
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