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AMPKα

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https://www.readbyqxmd.com/read/28225087/ampk-deficiency-in-chondrocytes-accelerated-the-progression-of-instability-induced-and-ageing-associated-osteoarthritis-in-adult-mice
#1
Sheng Zhou, Wanli Lu, Liang Chen, Qiting Ge, Dongyang Chen, Zhihong Xu, Dongquan Shi, Jin Dai, Jianxin Li, Huangxian Ju, Yi Cao, Jinzhong Qin, Shuai Chen, Huajian Teng, Qing Jiang
Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28214826/emodin-increases-expression-of-insulin-like-growth-factor-binding-protein-1-through-activation-of-mek-erk-ampk%C3%AE-and-interaction-of-ppar%C3%AE-and-sp1-in-lung-cancer
#2
Qing Tang, JingJing Wu, Fang Zheng, Swei Sunny Hann, YuQing Chen
BACKGROUND: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#3
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28129682/metformin-alleviates-lipopolysaccharide-induced-acute-lung-injury-through-suppressing-toll-like-receptor-4-signaling
#4
Haleh Vaez, Moslem Najafi, Negisa Seyed Toutounchi, Jaleh Barar, Abolfazl Barzegari, Alireza Garjani
Signaling AMP-activated protein kinase (AMPK), an energy sensing enzyme, has been implicated in controlling inflammation. In this study we investigated whether activation of AMPK by metformin could protect the lung from lipopolysaccharide (LPS)-induced acute injury by inhibitingng TLR4 pathway. Male Wistar rats were randomly divided into 3 groups (n=6): control group received normal saline (0.5 mL), LPS group received LPS (0.5 mg/kg), and metformin-treated group received LPS and metformin (100 mg/kg). Nine hours later nuclear factor-κB (NF-κB), phosphorylated, and non-phosphorylated AMPK using western blot, and the rate of TLR4 mRNA expression using real-time PCR were assessed in the lung tissue...
December 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28125642/gdm-induced-macrosomia-is-reversed-by-cav-1-via-ampk-mediated-fatty-acid-transport-and-glut1-mediated-glucose-transport-in-placenta
#5
Guo Yao, Yafang Zhang, Di Wang, Ruirui Yang, Hui Sang, Linlin Han, Yuexia Zhu, Yanyan Lu, Yeke Tan, Zhanping Shang
OBJECTIVE: To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. METHODS: We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups...
2017: PloS One
https://www.readbyqxmd.com/read/28123944/celastrol-ameliorates-liver-metabolic-damage-caused-by-a-high-fat-diet-through-sirt1
#6
Yinliang Zhang, Chao Geng, Xiaoyan Liu, Meixia Li, Mingyue Gao, Xiaojun Liu, Fude Fang, Yongsheng Chang
OBJECTIVE: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. METHODS: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. RESULTS: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28119079/deltamethrin-increases-the-fat-accumulation-in-3t3-l1-adipocytes-and-caenorhabditis-elegans
#7
Peiyi Shen, Tsung-Hsiu Hsieh, Yiren Yue, Quancai Sun, John M Clark, Yeonhwa Park
Research has shown that permethrin, a Type-I pyrethroid, increases triglyceride (fat) accumulation in adipocytes. Little is known, however, about any similar effect of deltamethrin, a Type-II pyrethroid, which produces a distinct syndrome of poisoning in mammals compared with permethrin. This study was therefore aimed to explore the role of deltamethrin on fat accumulation in 3T3-L1 adipocytes and Caenorhabditis elegans. Deltamethrin (10 μM) significantly increased the fat accumulation in 3T3-L1 adipocytes and wild type C...
January 22, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28118076/targeting-ampk-ulk1-mediated-autophagy-for-combating-bet-inhibitor-resistance-in-acute-myeloid-leukemia-stem-cells
#8
Ji Eun Jang, Ju-In Eom, Hoi-Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. We evaluated the levels of apoptosis and macroautophagy/autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+) CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28104351/the-sphingosine-1-phosphate-receptor-1-agonist-sew2871-reduces-tau-ser262-phosphorylation-in-rat-hippocampal-slices
#9
Frédéric St-Cyr Giguère, Suzanne Attiori Essis, Laure Chagniel, Marc Germain, Michel Cyr, Guy Massicotte
Recent studies indicate that Tau phosphorylation can be modulated by the compound FTY720-P, a global sphingosine-1-phosphate receptor (S1PR) agonist. The present work compared the effects of more selective S1PR agonists on Tau properties, using rat hippocampal slices as model system. Whereas Tau phosphorylation was not modified by the S1PR3 agonist CYM5541, Tau-Ser262 phosphorylation was significantly decreased by treatment with the S1PR1 agonist SEW2871. This effect appears to be quite restricted, as no changes in phosphorylation were elicited by the agonist on Tau-Ser199/202, Tau-Ser396 and Tau-Ser404 residues...
January 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28098516/germacrone-attenuates-hyperlipidemia-and-improves-lipid-metabolism-in-high-fat-diet-induced-obese-c57bl-6j-mice
#10
Yuan-Ri Guo, Se-Young Choung
We previously showed that Aster spathulifolius Maxim extract (ASE) reduced body weight gain and serum and liver lipid levels and significantly suppressed serum insulin and leptin concentrations in high-fat diet (HFD)-induced obese rats. Germacrone (GM) was identified as a potent bioactive constituent of ASE. In this study, we hypothesized that GM can attenuate hyperlipidemia by alleviating fatty acid (FA) synthesis/uptake and improve lipid metabolism by stimulating FA β-oxidation in HFD-induced obese C57BL/6J mice...
January 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28064564/aspartate-inhibits-lps-induced-mafbx-and-murf1-expression-in-skeletal-muscle-in-weaned-pigs-by-regulating-akt-ampk%C3%AE-and-foxo1
#11
Yulan Liu, Xiuying Wang, Weibo Leng, Dingan Pi, Zhixiao Tu, Huiling Zhu, Haifeng Shi, Shuang Li, Yongqing Hou, Chien-An Andy Hu
Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline...
January 2017: Innate Immunity
https://www.readbyqxmd.com/read/28061838/cryptotanshinone-activates-ampk-tsc2-axis-leading-to-inhibition-of-mtorc1-signaling-in-cancer-cells
#12
Wenxing Chen, Yanhong Pan, Siliang Wang, Yuping Liu, Guangying Chen, Liang Zhou, Wenting Ni, Aiyun Wang, Yin Lu
BACKGROUND: Cryptotanshinone (CPT), a fat-soluble phenanthraquinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), a couple of direct downstream effectors of the mammalian target of rapamycin complex 1 (mTORC1), resulting in cancer cell arrested in G0 phase and subsequent inhibition of proliferation. However, its concrete molecular mechanism about how CPT inhibits mTORC1 signaling pathway is unclear...
January 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28059052/gastrin-enhances-autophagy-and-promotes-gastric-carcinoma-proliferation-via-inducing-ampk%C3%AE
#13
Zhuang Kun, Guo Hanqing, Tang Hailing, Yan Yuan, Zhang Jun, Zhang Lingxia, Han Kun, Zhang Xin
Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells and it also plays a vital role in the development and progression of gastric cancer. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating gastric cancer tumorigenesis. Gastrin-17 amide (G-17) was applied in the gastric cancer cell lines SGC7901 and MGC-803...
January 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28052030/the-angiotensin-ii-type-1-receptor-antagonist-telmisartan-inhibits-cell-proliferation-and-tumor-growth-of-esophageal-adenocarcinoma-via-the-ampk%C3%AE-mtor-pathway-in-vitro-and-in-vivo
#14
Shintaro Fujihara, Asahiro Morishita, Kana Ogawa, Tomoko Tadokoro, Taiga Chiyo, Kiyohito Kato, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Tsutomu Masaki
Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28043053/the-decay-of-redox-stress-response-capacity-is-a-substantive-characteristic-of-aging-revising-the-redox-theory-of-aging
#15
Jiao Meng, Zhenyu Lv, Xinhua Qiao, Xiaopeng Li, Yazi Li, Yuying Zhang, Chang Chen
Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28018360/atp-induced-inflammasome-activation-and-pyroptosis-is-regulated-by-amp-activated-protein-kinase-in-macrophages
#16
Qing-Bing Zha, Hong-Xia Wei, Chen-Guang Li, Yi-Dan Liang, Li-Hui Xu, Wen-Jing Bai, Hao Pan, Xian-Hui He, Dong-Yun Ouyang
Adenosine triphosphate (ATP) is released by bacteria and host cells during bacterial infection as well as sterile tissue injury, acting as an inducer of inflammasome activation. Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. However, it is unclear whether AMPK signaling has been involved in the regulation of ATP-induced inflammasome activation and subsequent pyroptosis. In this study, we aimed to investigate this issue in lipopolysaccharide-activated murine macrophages...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28008317/chrysophanic-acid-suppresses-adipogenesis-and-induces-thermogenesis-by-activating-amp-activated-protein-kinase-alpha-in-vivo-and-in-vitro
#17
Hara Lim, Jinbong Park, Hye-Lin Kim, JongWook Kang, Mi-Young Jeong, Dong-Hyun Youn, Yunu Jung, Yong-Il Kim, Hyun-Ju Kim, Kwang Seok Ahn, Su-Jin Kim, Seong-Kyu Choe, Seung-Heon Hong, Jae-Young Um
Chrysophanic acid (CA) is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD)-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27980220/berberine-augments-atp-induced-inflammasome-activation-in-macrophages-by-enhancing-ampk-signaling
#18
Chen-Guang Li, Liang Yan, Yan-Yun Jing, Li-Hui Xu, Yi-Dan Liang, Hong-Xia Wei, Bo Hu, Hao Pan, Qing-Bing Zha, Dong-Yun Ouyang, Xian-Hui He
The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27978459/le-carbone-a-charcoal-supplement-modulates-dss-induced-acute-colitis-in-mice-through-activation-of-ampk%C3%AE-and-downregulation-of-stat3-and-caspase-3-dependent-apoptotic-pathways
#19
Mst Rejina Afrin, Somasundaram Arumugam, Md Azizur Rahman, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Takashi Nakamura, Shizuka Miyashita, Kenji Suzuki, Kazuyuki Ueno, Kenichi Watanabe
Le Carbone (LC) is a charcoal supplement, which contains a large amount of dietary fibers. Several studies suggested that charcoal supplement may be beneficial for stomach disorders, diarrhea, gas and indigestion. But no studies address whether LC intake would suppress inflammation, cell proliferation or disease progression in colitis. In the present study, the effect of LC on experimental colitis induced by dextran sulfate sodium (DSS) in mice and its possible mechanism of action were examined. A study was designed for 8days, using C57BL/6 female mice that were administered with 3% DSS in drinking water for 7days followed by another 1day consumption of normal water with or without treatment...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27960282/imidacloprid-promotes-high-fat-diet-induced-adiposity-and-insulin-resistance-in-male-c57bl-6j-mice
#20
Quancai Sun, Xiao Xiao, Yoo Kim, Daeyoung Kim, Kyoon Sup Yoon, John M Clark, Yeonhwa Park
Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity...
December 14, 2016: Journal of Agricultural and Food Chemistry
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