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https://www.readbyqxmd.com/read/28817623/metformin-attenuates-myocardial-ischemia-reperfusion-injury-via-up-regulation-of-antioxidant-enzymes
#1
Xiaoling Wang, Lei Yang, Licheng Kang, Jing Li, Liang Yang, Jincai Zhang, Jie Liu, Mengmeng Zhu, Qiong Zhang, Yanna Shen, Zhi Qi
The objective was to examine the protective effect of metformin (Met) on myocardial ischemia-reperfusion (IR) injury and whether the mechanism was related to the AMPK/ antioxidant enzymes signaling pathway. Rat Langendorff test and H2O2-treated rat cardiomyocytes (H9c2) were used in this study. Met treatment significantly improved left ventricular (LV) function, reduced infarct size and CK-MB release in comparison with IR group. Decreased TUNEL staining positive cells were also observed in IR+Met group ex vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28813465/long-term-persistent-infection-of-hpv-16-e6-up-regulate-sp1-and-htert-by-inhibiting-lkb1-in-lung-cancer-cells
#2
Jing-Hua Yang, Xiao-Yan Li, Xin Wang, Wei-Jian Hou, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28801289/-lkb1-regulates-epithelial-mesenchymal-transition-in-peutz-jeghers-hamartoma-and-intestinal-epithelial-cells
#3
Chao Zhong, Liang Peng, Ran Li, Jing Chen, Xin-Qi Chen, Di Zeng, Xiao-Ping Xu, Zhi-Qing Wang, Chu-di Chen, Ya-Dong Wang, Ai-Min Li, Si-de Liu, Bao-Ping Wu
OBJECTIVE: To investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells. METHODS: Immunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28789977/ablation-of-systemic-sirt1-activity-promotes-nonalcoholic-fatty-liver-disease-by-affecting-liver-mesenteric-adipose-tissue-fatty-acid-mobilization
#4
Junrui Cheng, Chun Liu, Kangquan Hu, Andrew Greenberg, Dayong Wu, Lynne M Ausman, Michael W McBurney, Xiang-Dong Wang
Sirtuin 1 (SIRT1) has been reported to protect against nonalcoholic fatty liver disease (NAFLD) development. The mechanism of how SIRT1 deacetylase activity affects NAFLD has not been well investigated. The current investigation addressed the causal effect of systemic SIRT1 activity on NAFLD development and the underlying mechanism involved in both liver and mesenteric adipose tissue (MAT). Both SIRT1 homozygous mice ablated the catalytic activity (sirt1(Y/Y)) and their corresponding wild type littermates (WT) were fed a high fat diet (HFD, 60% calories from fat) for 34weeks...
August 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28767695/drosophila-lkb1-is-required-for-the-assembly-of-the-polarized-actin-structure-that-allows-spermatid-individualization
#5
Jean-Louis Couderc, Graziella Richard, Caroline Vachias, Vincent Mirouse
In mammals, a testis-specific isoform of the protein kinase LKB1 is required for spermiogenesis, but its exact function and specificity are not known. Human LKB1 rescues the functions of Drosophila Lkb1 essential for viability, but these males are sterile, revealing a new function for this genes in fly. We also identified a testis-specific transcript generated by an alternative promoter and that only differs by a longer 5'UTR. We show that dLKB1 is required in the germline for the formation of the actin cone, the polarized structure that allows spermatid individualization and cytoplasm excess extrusion during spermiogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28766983/lkb1-ampk-modulates-nutrient-induced-changes-in-the-mode-of-division-of-intestinal-epithelial-crypt-cells-in-mice
#6
Katherine Blackmore, Weinan Zhou, Megan J Dailey
Nutrient availability influences intestinal epithelial stem cell proliferation and tissue growth. Increases in food result in a greater number of epithelial cells, villi height and crypt depth. We investigated whether this nutrient-driven expansion of the tissue is the result of a change in the mode of intestinal epithelial stem cell division and if LKB1-AMPK signaling plays a role. We utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice were separated into four groups and fed varying amounts of chow for 18 h: (1) ad libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h and refed...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28766947/creatine-monohydrate-enhances-energy-status-and-reduces-glycolysis-via-inhibition-of-ampk-pathway-in-pectoralis-major-muscle-of-transport-stressed-broilers
#7
Lin Zhang, Xiaofei Wang, Jiaolong Li, Xudong Zhu, Feng Gao, Guanghong Zhou
Creatine monohydrate (CMH) contributes to reduce transport-induced muscle rapid glycolysis and improve meat quality of broilers, but the underlying mechanism is still unknown. Therefore, this study aimed to investigate the molecular mechanisms underlying the ameliorative effects of CMH on muscle glycolysis metabolism of transported broilers during summer. The results showed that 3 h transport during summer elevated chicken live weight loss and plasma corticosterone concentration; decreased muscle concentrations of ATP, creatine, and energy charge value; increased muscle AMP concentration and AMP/ATP ratio; and upregulated muscle mRNA expression of LKB1 and AMPKα2, as well as protein expression of p-LKB1(Thr189) and p-AMPKα(Thr172), which subsequently resulted in rapid glycolysis in the pectoralis major muscle and consequent reduction of meat quality...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28761738/results-of-the-safety-run-in-part-of-the-metal-metformin-in-advanced-lung-cancer-study-a-multicentre-open-label-phase-i-ii-study-of-metformin-with-erlotinib-in-second-line-therapy-of-patients-with-stage-iv-non-small-cell-lung-cancer
#8
Floriana Morgillo, Morena Fasano, Carminia Maria Della Corte, Ferdinando Carlo Sasso, Federica Papaccio, Giuseppe Viscardi, Giovanna Esposito, Raimondo Di Liello, Nicola Normanno, Annalisa Capuano, Liberato Berrino, Giovanni Vicidomini, Alfonso Fiorelli, Mario Santini, Fortunato Ciardiello
PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene...
2017: ESMO Open
https://www.readbyqxmd.com/read/28754670/gemcitabine-and-chk1-inhibitor-azd7762-synergistically-suppress-the-growth-of-lkb1-deficient-lung-adenocarcinoma
#9
Kwok-Kin Wong, Yan Liu, Yuyang Li, Xiaoen Wang, Feiyang Liu, Peng Gao, Max M Quinn, Fei Li, Ashley A Merlino, Cyril H Benes, Qingsong Liu, Nathanael S Gray
Cells lacking the tumor suppressor gene LKB1/STK11 alter their metabolism to match the demands of accelerated growth, leaving them highly vulnerable to stress. However, targeted therapy for LKB1-deficient cancers has yet to be reported. In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model (GEMM) of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA damage occur resulting in increased dependence on Chk1 checkpoint function. Here we demonstrate that short-term treatment with the Chk1 inhibitor AZD7762 reduces metabolism in Kras/p53/Lkb1 tumors, synergizing with the DNA damaging drug gemcitabine to reduce tumor size in these models...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28743498/hydrogen-rich-medium-protects-mouse-embryonic-fibroblasts-from-oxidative-stress-by-activating-lkb1-ampk-foxo1-signal-pathway
#10
Jihyun Lee, Goowon Yang, Young-Joo Kim, Tran Quynh Hoa, Wonchae Choe, Insug Kang, Sung Soo Kim, Joohun Ha
Persistent oxidative stress is recognized as a major cause of many pathological conditions as well as ageing. However, most clinical trials of dietary antioxidants have failed to produce successful outcomes in treating oxidative stress-induced diseases. Molecular hydrogen (H2) has recently received considerable attention as a therapeutic agent owing to its novel antioxidant properties, a selective scavenger of hydroxyl and peroxynitrite radicals. Beyond this, numerous reports support that H2 can modulate the activity of various cellular signal pathways...
July 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28736255/isoalantolactone-derivative-promotes-glucose-utilization-in-skeletal-muscle-cells-and-increases-energy-expenditure-in-db-db-mice-via-activating-ampk-dependent-signaling
#11
Deepti Arha, E Ramakrishna, Anand P Gupta, Amit K Rai, Aditya Sharma, Ishbal Ahmad, Mohammed Riyazuddin, Jiaur R Gayen, Rakesh Maurya, Akhilesh K Tamrakar
Augmenting glucose utilization and energy expenditure in skeletal muscle via AMP-activated protein kinase (AMPK) is an imperative mechanism for the management of type 2 diabetes. Chemical derivatives (2a-2h, 3, 4a-4d, 5) of the isoalantolactone (K007), a bioactive molecule from roots of Inula racemosa were synthesized to optimize the bioactivity profile to stimulate glucose utilization in skeletal muscle cells. Interestingly, 4a augmented glucose uptake, driven by enhanced translocation of glucose transporter 4 (GLUT4) to cell periphery in L6 rat skeletal muscle cells...
July 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28732195/fake-inhibitors-ampk-activation-trumps-inhibition
#12
Christopher G Langendorf, John W Scott, Bruce E Kemp
Protein kinase inhibitors have become increasingly important therapeutic drugs for the treatment of human diseases; however, resistance and off-target effects can limit their use. In this issue of Cell Chemical Biology, Ross et al. (2017) reveal a novel off-target mechanism where the Src kinase inhibitor SU6656 paradoxically primes AMPK for phosphorylation and activation by the upstream kinase LKB1.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28723898/fructose-1-6-bisphosphate-and-aldolase-mediate-glucose-sensing-by-ampk
#13
Chen-Song Zhang, Simon A Hawley, Yue Zong, Mengqi Li, Zhichao Wang, Alexander Gray, Teng Ma, Jiwen Cui, Jin-Wei Feng, Mingjiang Zhu, Yu-Qing Wu, Terytty Yang Li, Zhiyun Ye, Shu-Yong Lin, Huiyong Yin, Hai-Long Piao, D Grahame Hardie, Sheng-Cai Lin
The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease...
August 3, 2017: Nature
https://www.readbyqxmd.com/read/28720067/hpv16-e6-e7-upregulates-hif-2%C3%AE-and-vegf-by-inhibiting-lkb1-in-lung-cancer-cells
#14
Jian-Shuang Shao, Jian Sun, Shiyu Wang, Katherine Chung, Jin Tong Du, Jason Wang, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28708087/resveratrol-induced-amp-activated-protein-kinase-activation-is-cell-type-dependent-lessons-from-basic-research-for-clinical-application
#15
Fan Lan, Karen A Weikel, Jose M Cacicedo, Yasuo Ido
Despite the promising effects of resveratrol, its efficacy in the clinic remains controversial. We were the first group to report that the SIRT1 activator resveratrol activates AMP-activated protein kinase (AMPK) (Diabetes 2005; 54: A383), and we think that the variability of this cascade may be responsible for the inconsistency of resveratrol's effects. Our current studies suggest that the effect of SIRT1 activators such as resveratrol may not be solely through activation of SIRT1, but also through an integrated effect of SIRT1-liver kinase B1 (LKB1)-AMPK...
July 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28701883/20s-protopanaxadiol-an-aglycosylated-ginsenoside-metabolite-induces-hepatic-stellate-cell-apoptosis-through-liver-kinase-b1-amp-activated-protein-kinase-activation
#16
Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A Park, Il Je Cho, Sang Chan Kim
BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#17
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28696138/adipoq-adiponectin-induces-cytotoxic-autophagy-in-breast-cancer-cells-through-stk11-lkb1-mediated-activation-of-the-ampk-ulk1-axis
#18
Seung J Chung, Ganji Purnachandra Nagaraju, Arumugam Nagalingam, Nethaji Muniraj, Panjamurthy Kuppusamy, Alyssa Walker, Juhyung Woo, Balázs Győrffy, Ed Gabrielson, Neeraj K Saxena, Dipali Sharma
ADIPOQ/adiponectin, an adipocytokine secreted by adipocytes in the breast tumor microenvironment, negatively regulates cancer cell growth hence increased levels of ADIPOQ/adiponectin are associated with decreased breast cancer growth. However, its mechanisms of action remain largely elusive. We report that ADIPOQ/adiponectin induces a robust accumulation of autophagosomes, increases MAP1LC3B-II/LC3B-II and decreases SQSTM1/p62 in breast cancer cells. ADIPOQ/adiponectin-treated cells and xenografts exhibit increased expression of autophagy-related proteins...
July 11, 2017: Autophagy
https://www.readbyqxmd.com/read/28694351/phosphorylation-of-ampk-by-upstream-kinases-is-required-for-activity-in-mammalian-cells
#19
Robin Willows, Matthew J Sanders, Bing Xiao, Bhakti R Patel, Stephen R Martin, Jon Read, Jon R Wilson, Julia Hubbard, Steven J Gamblin, David Carling
AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism and has attracted significant attention as a therapeutic target for treating metabolic disorders. AMPK activity is stimulated more than one hundred fold by phosphorylation of threonine 172 (Thr(172)). Binding of AMP to the γ subunit allosterically activates the kinase. Additionally, a number of small molecules e.g. 991, have been identified that bind between the kinase domain and the carbohydrate binding module of the β subunit, stabilising their interaction and leading to activation...
July 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28694192/laminar-shear-stress-suppresses-vascular-smooth-muscle-cell-proliferation-through-nitric-oxide-ampk-pathway
#20
Sun Ae Kim, Jin Young Sung, Chang-Hoon Woo, Hyoung Chul Choi
In healthy condition, vascular smooth muscle cells (VSMCs) are not directly exposed to shear stresses, because they are shielded by endothelial cell (EC) layer that lines blood vessels. After injury to EC layer caused by rupture of atherosclerotic lesions or invasive techniques such as angioplasty, VSMCs are directly exposed to blood flow which modulate molecular signaling and function. In endothelium, exposure to fluid shear stress has been reported to induce AMP-activated protein kinase (AMPK) phosphorylation and nitric oxide (NO) production...
September 2, 2017: Biochemical and Biophysical Research Communications
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