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https://www.readbyqxmd.com/read/28636994/a-novel-ampk-activator-hernandezine-inhibits-lps-induced-tnf%C3%AE-production
#1
Ping Li, Xiaofang Li, Yonghong Wu, Manxiang Li, Xiaochuang Wang
Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#2
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28602729/alpha-lipoic-acid-impairs-body-weight-gain-of-young-broiler-chicks-via-modulating-peripheral-ampk
#3
Yufeng Wang, Nadia Everaert, Zhigang Song, Eddy Decuypere, Daniel Vermeulen, Johan Buyse
In mammals, the AMP-activated protein kinase (AMPK) pathways in the central and peripheral tissues coordinately integrate inputs from multiple sources to regulate energy balance. The present study was aimed to explore the potential role of hepatic AMPK in the energy homeostasis of broiler chickens. Diets with 0, 0.05% or 0.1% alpha-lipoic acid (α-LA), a known AMPK inhibitor were provided to broiler chicks for 7days. As a result, α-LA supplementation decreased the relative growth rate of broiler chicks. Hepatic AMPKα2 mRNA levels were significantly upregulated by dietary α-LA, in concert with the increased phosphorylated AMPKα protein levels...
June 8, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28600551/epe1-contributes-to-activation-of-ampk-by-promoting-phosphorylation-of-ampk-alpha-subunit-ssp2
#4
Yongyi Chen, Xiaoyue Hu, Chao Guo, Yao Yu, Hong Lu
AMP-activated protein kinase (AMPK) is a pivotal cellular energy sensor. It is activated by stresses that cause depletion of energy and initiates adaptive responses by regulating metabolism balance. AMPK forms αβγ heterotrimer. In fission yeast, activation of AMPK mainly depends on the phosphorylation of AMPKα subunit Ssp2 at Thr(189) by upstream kinase Ssp1. However, not much is known about the regulation of this process. In this study, we identified Epe1 as a novel positive regulator of AMPK. Epe1, a jmjC-domain-containing protein, is best-known as a negative regulator of heterochromatin spreading...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600513/trpc5-induced-autophagy-promotes-drug-resistance-in-breast-carcinoma-via-camkk%C3%AE-ampk%C3%AE-mtor-pathway
#5
Peng Zhang, Xiaoyu Liu, Hongjuan Li, Zhen Chen, Xiaoqiang Yao, Jian Jin, Xin Ma
Adriamycin is a first-line chemotherapy agent against cancer, but the development of resistance has become a major problem. Although autophagy is considered to be an adaptive survival response in response to chemotherapy and may be associated with chemoresistance, its inducer and the underlying molecular mechanisms remain unclear. Here, we demonstrate that adriamycin up-regulates the both levels of TRPC5 and autophagy, and the increase in autophagy is mediated by TRPC5 in breast cancer cells. Blockade of TRPC5 or autophagy increased the sensitivity to chemotherapy in vitro and in vivo...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588681/effects-of-gui-zhu-yi-kun-formula-on-the-p53-ampk-pathway-of-autophagy-in-granulosa-cells-of-rats-with-polycystic-ovary-syndrome
#6
Yu Xing, Yan-Xia Liu, Xin Liu, Shu-Lin Wang, Ping Li, Xiao-Hua Lin, Cong-Lu Sui, Cai Xu, Bing Qi, Qing Tong
The aim of the present study was to investigate the molecular mechanism associated with the traditional Chinese medicine formula Gui Zhu Yi Kun formula (GZYKF), in the treatment of polycystic ovary syndrome (PCOS). In this study, granulosa cells (GCs) of rats with PCOS were cultured and treated with testosterone propionate (TP) alone or with serum from rats treated with different doses of GZYKF. The effect of TP on cell growth was assayed using the MTT method. Expression levels of Beclin-1, light chain (LC)3, mechanistic target of rapamycin (mTOR), tumor suppressor p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), sestrin2 and tuberous sclerosis protein 1/2 were evaluated using quantitative polymerase chain reaction and western blotting...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580173/sesn2-gene-ablation-enhances-susceptibility-to-gentamicin-induced-hair-cell-death-via-modulation-of-ampk-mtor-signaling
#7
Eliane Ebnoether, Alessia Ramseier, Maurizio Cortada, Daniel Bodmer, Soledad Levano-Huaman
The process of gentamicin-induced hair cell damage includes the activation of oxidative stress processes. Sestrins, as stress-responsive proteins, protect cells against oxidative stress. Sestrins, particularly Sestrin-2, suppress excessive reactive oxygen species (ROS) accumulation and inhibit mammalian target of rapamycin complex 1 (mTORC1). Thus, we addressed the role of Sestrin-2 in the regulation of sensory hair cell survival after gentamicin exposure. Here, we show that Sestrins were expressed in the inner ear tissues, and Sestrin-2 immunolocalized in sensory hair cells and spiral ganglion (SG)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28579457/metformin-ameliorates-gender-and-age-dependent-hemodynamic-instability-and-myocardial-injury-in-murine-hemorrhagic-shock
#8
Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli
Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28572154/novel-role-of-npy-in-neuro-immune-interaction-and-lung-growth-after-intrauterine-growth-restriction
#9
Chansutha Thangaratnarajah, Katharina Dinger, Christina Vohlen, Christian Klaudt, Jawed Nawabi, Eva Lopez Garcia, Grazyna Kwapiszewska, Julia Dobner, Kai D Nuesken, Silke van Koningsbruggen-Rietschel, Stephan von Hoersten, Jörg Dötsch, Miguel Angel Alejandre Alcazar
Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, our previous studies showed that altered lung structure is related to IL-6/STAT3 signaling. As Neuropeptide Y (NPY), a co-neurotransmitter of the sympathetic nerve system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12 and P23...
June 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28546220/activation-of-adiponectin-receptor-regulates-proprotein-convertase-subtilisin-kexin-type-9-expression-and-inhibits-lesions-in-apoe-deficient-mice
#10
Lei Sun, Xiaoxiao Yang, Qi Li, Peng Zeng, Ying Liu, Lipei Liu, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Yan Li, Rongxin Zhang, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
OBJECTIVE: The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28532828/expression-of-apelin-and-apelin-receptor-apj-in-porcine-ovarian-follicles-and-in%C3%A2-vitro-effect-of-apelin-on-steroidogenesis-and-proliferation-through-apj-activation-and-different-signaling-pathways
#11
A Rak, E Drwal, Ch Rame, K Knapczyk-Stwora, M Słomczyńska, J Dupont, E L Gregoraszczuk
Apelin was thought to be an adipocyte-specific hormone, but recent studies indicate a link between apelin and female reproductive function. Using real-time PCR, immunoblotting, immunohistochemistry and ELISA, we demonstrated expression of apelin and its receptor (APJ) in ovarian follicles of different sizes from mature pigs. Apelin concentration in the follicular fluid, and expression of both apelin and APJ, increased with follicular growth; greatest values were found in large follicles. Immunohistochemistry revealed the positive staining for apelin and APJ in membranes of granulosa, than theca cells...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28515080/effect-of-resistance-exercise-under-conditions-of-reduced-blood-insulin-on-ampk%C3%AE-ser485-491-inhibitory-phosphorylation-and-ampk-pathway-activation
#12
Kohei Kido, Takumi Yokokawa, Satoru Ato, Koji Sato, Satoshi Fujita
Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin down-regulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus, lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation...
May 17, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28502303/-effect-of-metformin-on-proliferation-and-apoptosis-of-rat-prolactinoma-mmq-cells-and-related-mechanisms
#13
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mou, Gang Yang
Objective To investigate the effect of metformin on the cell proliferation, cell cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation ability; flow cytometry was used to analyze the cell cycle distribution and apoptosis; Western blotting was performed to detect the expressions of AMPKα1/2, p-AMPKα, mTOR, p-mTOR, insulin like growth factor 1 receptor (IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved caspase-3(c-caspase-3), Bcl-2 and BAX...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28496133/folate-metabolism-regulates-oligodendrocyte-survival-and-differentiation-by-modulating-ampk%C3%AE-activity
#14
Qinjie Weng, Jiajia Wang, Jiaying Wang, Biqin Tan, Jing Wang, Haibo Wang, Tao Zheng, Q Richard Lu, Bo Yang, Qiaojun He
Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism for many cellular pathways including DNA synthesis, metabolism and maintenance. Folate deficiency has been associated with an increased risk of neurological disease, cancer and cognitive dysfunction. Dihydrofolate reductase (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR activity in oligodendrocyte development has not been fully understood. Here we show that folate enhances oligodendrocyte maturation both in vitro and in vivo, which is accompanied with upregulation of oligodendrocyte-specific DHFR expression...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494245/global-reprogramming-of-host-kinase-signaling-in-response-to-fungal-infection
#15
Aseem Pandey, Sheng Li Ding, Qing-Ming Qin, Rahul Gupta, Gabriel Gomez, Furong Lin, Xuehuan Feng, Luciana Fachini da Costa, Sankar P Chaki, Madhu Katepalli, Elizabeth D Case, Erin J van Schaik, Tabasum Sidiq, Omar Khalaf, Angela Arenas, Koichi S Kobayashi, James E Samuel, Gonzalo M Rivera, Robert C Alaniz, Sing-Hoi Sze, Xiaoning Qian, William J Brown, Allison Rice-Ficht, William K Russell, Thomas A Ficht, Paul de Figueiredo
Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28483572/early-energy-metabolism-related-molecular-events-in-skeletal-muscle-of-diabetic-rats-the-effects-of-l-arginine-and-sod-mimic
#16
Ana Stancic, Milos Filipovic, Ivana Ivanovic-Burmazovic, Sava Masovic, Aleksandra Jankovic, Vesna Otasevic, Aleksandra Korac, Biljana Buzadzic, Bato Korac
Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28459610/3-3-diindolylmethane-suppresses-adipogenesis-using-ampk%C3%AE-dependent-mechanism-in-3t3-l1-adipocytes-and-caenorhabditis-elegans
#17
Jihye Lee, Yiren Yue, Yeonhwa Park, Seong-Ho Lee
3,3'-diindolylmethane is a major in vivo metabolite of indole-3-carbinol, a bioactive compound found in cruciferous vegetables. Although 3,3'-diindolylmethane has been implicated to possess antitumorigenic and anti-inflammatory properties, the effect of 3,3'-diindolylmethane on adipogenesis has not been explored previously. Thus, the present study was conducted to determine if 3,3'-diindolylmethane affects adipogenesis using 3T3-L1 adipocytes and Caenorhabditis elegans. Treatment of 3,3'-diindolylmethane significantly reduced fat accumulation without affecting viability in 3T3-L1 adipocytes...
May 1, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28449683/inhibition-of-nampt-aggravates-high-fat-diet-induced-hepatic-steatosis-in-mice-through-regulating-sirt1-ampk%C3%AE-srebp1-signaling-pathway
#18
Ling-Fang Wang, Xiao-Nv Wang, Cong-Cong Huang, Long Hu, Yun-Fei Xiao, Xiao-Hui Guan, Yi-Song Qian, Ke-Yu Deng, Hong-Bo Xin
BACKGROUND: Nonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD(+)) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis...
April 27, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28445531/antagomir-451-inhibits-oxygen-glucose-deprivation-ogd-induced-huvec-necrosis-via-activating-ampk-signaling
#19
Xi Yang, Xiao-Qing He, Guo-Dong Li, Yong-Qing Xu
Oxygen glucose deprivation (OGD) application in cultured human umbilical vein endothelial cells (HUVECs) mimics ischemic injuries. AntagomiR-451, the miroRNA-451 ("miR-451") inhibitor, could activate pro-survival AMP-activated protein kinase (AMPK) signaling. In the current study, we showed that forced-expression of antagomiR-451 depleted miRNA-451 and significantly attenuated OGD-induced necrosis of HUVECs. Activation of AMPK was required for antagomiR-451-mediated pro-survival actions. AMPK inhibition, by AMPKα shRNA or dominant negative mutation, almost completely abolishedantagomiR-451-mediated HUVEC protection again OGD...
2017: PloS One
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#20
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
June 2017: International Journal of Oncology
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