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https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#1
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29325553/sitagliptin-improved-glucose-assimilation-in-detriment-of-fatty-acid-utilization-in-experimental-type-ii-diabetes-role-of-glp-1-isoforms-in-glut4-receptor-trafficking
#2
E Ramírez, B Picatoste, A González-Bris, M Oteo, F Cruz, A Caro-Vadillo, J Egido, J Tuñón, M A Morcillo, Ó Lorenzo
BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG)...
January 11, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29284690/ampk%C3%AE-2-protects-against-the-development-of-heart-failure-by-enhancing-mitophagy-via-pink1-phosphorylation
#3
Bei Wang, Jiali Nie, Lujin Wu, Yangyang Hu, Zeng Wen, Lingli Dong, Ming-Hui Zou, Chen Chen, Dao Wen Wang
Rationale: Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood. Objective: We sought to determine the role of AMP-activated protein kinase (AMPK) in selective mitophagy during HF. Methods and Results: An isoform shift from AMPKα2 to AMPKα1 was observed in failing-heart samples from HF patients and transverse aortic constriction (TAC)-induced mice, accompanied by decreased mitophagy and mitochondrial function...
December 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/29284117/knockdown-of-ampk%C3%AE-decreases-atm-expression-and-increases-radiosensitivity-under-hypoxia-and-nutrient-starvation-in-an-sv40-transformed-human-fibroblast-cell-line-lm217
#4
Yasuhiko Murata, Takuma Hashimoto, Yusuke Urushihara, Soichiro Shiga, Kazuya Takeda, Keiichi Jingu, Yoshio Hosoi
BACKGROUND: Presence of unperfused regions containing cells under hypoxia and nutrient starvation contributes to radioresistance in solid human tumors. It is well known that hypoxia causes cellular radioresistance, but little is known about the effects of nutrient starvation on radiosensitivity. We have reported that nutrient starvation induced decrease of mTORC1 activity and decrease of radiosensitivity in an SV40-transformed human fibroblast cell line, LM217, and that nutrient starvation induced increase of mTORC1 activity and increase of radiosensitivity in human liver cancer cell lines, HepG2 and HuH6 (Murata et al...
December 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29241574/glucose-mediated-inactivation-of-amp-activated-protein-kinase-reduces-the-levels-of-l-type-amino-acid-transporter-1-mrna-in-c2c12-cells
#5
Yu Yamamoto, Ran Sawa, Ikumi Wake, Ayaka Morimoto, Yasuhiko Okimura
Branched chain amino acids (BCAAs) have protective effects against muscle atrophy. Although plasma BCAA concentrations are higher in patients with diabetes than in healthy subjects, diabetes is related to sarcopenia. We hypothesized that high glucose concentration reduces the quantity of BCAA transporters, and consequently, the effects of BCAAs are diminished despite their high levels. We examined whether glucose reduces the expression of L-type amino acid transporter 1 (LAT1), which transports neutral amino acids, including BCAA, in C2C12 myocytes...
November 2017: Nutrition Research
https://www.readbyqxmd.com/read/29221169/targeting-pp2a-activates-ampk-signaling-to-inhibit-colorectal-cancer-cells
#6
Cuiping Dai, Xuning Zhang, Da Xie, Peipei Tang, Chunmei Li, Yi Zuo, Baofei Jiang, Caiping Xue
LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC) cells was tested. The in vitro studies demonstrated that LB-100 inhibited survival and proliferation of both established CRC cells (HCT-116 and HT-29 lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity and activated AMPK signaling in CRC cells. AMPKα1 dominant negative mutation, shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217477/activation-of-hepatic-nogo-b-receptor-expression-a-new-anti-liver-steatosis-mechanism-of-statins
#7
Wenwen Zhang, Xiaoxiao Yang, Yuanli Chen, Wenquan Hu, Lipei Liu, Xiaomeng Zhang, Mengyang Liu, Lei Sun, Ying Liu, Miao Yu, Xiaoju Li, Luyuan Li, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29212325/chronic-heat-stress-impairs-meat-quality-of-breast-muscle-in-broilers-through-affecting-redox-status-and-energy-substances-metabolism
#8
Zhuang Lu, Xiaofang He, Bingbing Ma, Lin Zhang, Jiaolong Li, Yun Jiang, Guanghong Zhou, Feng Gao
We investigated the molecular mechanisms of chronic heat stress impairing broilers breast meat quality. Broilers were assigned to three groups including normal control (NC) group, heat stress (HS) group and pair-fed (PF) group. After 7d of heat exposure (32°C), high temperature caused oxidative stress, and elevated the activity of citrate synthase (CS), mRNA expression of M-CPT1, and phosphorylation level of AMPKα, and reduced the mRNA expression of avUCP. After 14d of heat exposure, heat stress increased lightness and drip loss and decreased pH and shear force of breast meat...
December 7, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29204135/recombinant-uncarboxylated-osteocalcin-per-se-enhances-mouse-skeletal-muscle-glucose-uptake-in-both-extensor-digitorum-longus-and-soleus-muscles
#9
Xuzhu Lin, Lewan Parker, Emma Mclennan, Xinmei Zhang, Alan Hayes, Glenn McConell, Tara C Brennan-Speranza, Itamar Levinger
Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29198236/acetate-alters-the-process-of-lipid-metabolism-in-rabbits
#10
C Fu, L Liu, F Li
An experiment was conducted to investigate the effect of acetate treatment on lipid metabolism in rabbits. New Zealand Rabbits (30 days, n=80) randomly received a subcutaneous injection (2 ml/injection) of 0, 0.5, 1.0 or 2.0 g/kg per day body mass acetate (dissolved in saline) for 4 days. Our results showed that acetate induced a dose-dependent decrease in shoulder adipose (P0.05), acetate treatment significantly decreased the plasma adiponectin, insulin and triglyceride concentrations (P<0.05). In adipose, acetate injection significantly up-regulated the gene expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), differentiation-dependent factor 1 (ADD1), adipocyte protein 2 (aP2), carnitine palmitoyltransferase 1 (CPT1), CPT2, hormone-sensitive lipase (HSL), G protein-coupled receptor (GPR41), GPR43, adenosine monophosphate-activated protein kinase α1 (AMPKα1), adiponectin receptor (AdipoR1), AdipoR2 and leptin receptor...
December 4, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29191621/propionibacterium-acnes-induces-autophagy-in-keratinocytes-involvement-of-multiple-mechanisms
#11
Klára Megyeri, László Orosz, Szilvia Bolla, Lilla Erdei, Zsolt Rázga, György Seprényi, Edit Urbán, Kornélia Szabó, Lajos Kemény
Propionibacterium acnes is a dominant member of the cutaneous microbiota. Herein, we evaluate the effects of different P. acnes strains and propionic acid on autophagy in keratinocytes. Our results showed that P. acnes strain 889 altered the architecture of the mitochondrial network, elevated the levels of LC3B-II, Beclin-1 and phospho-AMPKα, stimulated autophagic flux, facilitated intracellular redistribution of LC3B, increased average number of autophagosomes per cell, and enhanced development of acidic vesicular organelles in the HPV-KER cell line...
November 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29176803/root-bark-of-ulmus-davidiana-var-japonica-restrains-acute-alcohol-induced-hepatic-steatosis-onset-in-mice-by-inhibiting-ros-accumulation
#12
Jeong Hoon Pan, Yejin Lim, Jun Ho Kim, Wan Heo, Ki Yong Lee, Hye Ji Shin, Jae Kyeom Kim, Jin Hyup Lee, Young Jun Kim
Alcohol-induced hepatic steatosis and inflammation are key drivers of alcohol-induced liver injury, mainly caused by oxidative stress. The roots bark of Ulmus davidiana var. japonica is well known for its substantial antioxidative and antitumorigenic potency. In this study, we examined whether this plant can ameliorate alcohol-induced liver injuries characterized by hepatic steatosis and inflammation through its antioxidative activity. C57BL/6J mice were treated with the root bark extract of Ulmus davidiana var...
2017: PloS One
https://www.readbyqxmd.com/read/29173234/dietary-%C3%AE-lactalbumin-induced-fatty-liver-by-enhancing-nuclear-liver-x-receptor-%C3%AE-%C3%AE-sterol-regulatory-element-binding-protein-1c-ppar%C3%AE-expression-and-minimising-ppar%C3%AE-carnitine-palmitoyltransferase-1-expression-and-amp-activated-protein-kinase-%C3%AE-phosphorylation
#13
María Elvira López-Oliva, Alba Garcimartin, Emilia Muñoz-Martínez
The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment...
November 27, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29165897/lithospermum-erythrorhizon-root-and-its-naphthoquinones-repress-srebp1c-and-activate-pgc1%C3%AE-through-ampk%C3%AE
#14
Rodney A Velliquette, Arun Rajgopal, John Rebhun, Kelly Glynn
OBJECTIVE: To examine specific molecular mechanisms involved in modulating hepatic lipogenesis and mitochondria biogenesis signals by Lithospermum erythrorhizon (gromwell) root extract. METHODS: Stable cell lines with luciferase reporter constructs were generated to examine sterol regulatory element binding protein 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1) α promoter activity and estrogen-related receptor (ERR) α response element activity...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29165727/erratum-aucubin-protects-against-tgf%C3%AE-1-induced-cardiac-fibroblasts-activation-by-mediating-the-ampk%C3%AE-mtor-signaling-pathway
#15
Yang Xiao, Wei Chang, Qing-Qing Wu, Xiao-Han Jiang, Ming-Xia Duan, Ya-Ge Jin, Qi-Zhu Tang
No abstract text is available yet for this article.
November 17, 2017: Planta Medica
https://www.readbyqxmd.com/read/29158183/serine-prevented-high-fat-diet-induced-oxidative-stress-by-activating-ampk-and-epigenetically-modulating-the-expression-of-glutathione-synthesis-related-genes
#16
Xihong Zhou, Liuqin He, Shengnan Zuo, Yumei Zhang, Dan Wan, Ciming Long, Pan Huang, Canrong Wu, Xin Wu, Gang Liu, Yulong Yin
Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57BL/6J mice (9week-old) were randomly assigned into four groups (n=10) and fed: i) a low-fat diet; ii) a low-fat diet supplemented with 1% (wt:vol) serine; iii) a high-fat (HF) diet; and iv) a HF diet supplemented with 1% serine, respectively...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29141998/vanillic-acid-attenuates-obesity-via-activation-of-the-ampk-pathway-and-thermogenic-factors-in-vivo-and-in-vitro
#17
Yunu Jung, Jinbong Park, Hye-Lin Kim, Jung-Eun Sim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Woong Mo Yang, Seok-Geun Lee, Kwang Seok Ahn, Jae-Young Um
Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29113185/adenine-causes-cell-cycle-arrest-and-autophagy-of-chronic-myelogenous-leukemia-k562-cells-via-amp-activated-protein-kinase-signaling
#18
San-Yuan Chen, Chun-Hsiang Lin, Jiun-Tsai Lin, Yi-Fang Cheng, Han-Min Chen, Shao-Hsuan Kao
AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109024/ampk-regulates-immunometabolism-in-sepsis
#19
Jun Huang, Ke Liu, Shan Zhu, Min Xie, Rui Kang, Lizhi Cao, Daolin Tang
Sepsis and septic shock remain challenging for intensive care units worldwide and have limited treatment options; therefore, identification of targetable key players in systemic inflammation and multiple organ failure is urgently needed. Here, we show that AMP-activated protein kinase (AMPK) is a negative regulator of bioenergetic reprogramming in immune cells and suppresses sepsis development in vivo. Mechanistically, AMPK deficiency increases pyruvate kinase isozyme M2 (PKM2)-dependent aerobic glycolysis, which leads to the release of high mobility group box 1 (HMGB1, a late mediator of lethal systemic inflammation) in macrophages and monocytes...
November 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29100525/modulating-the-catalytic-activity-of-ampk-has-neuroprotective-effects-against-%C3%AE-synuclein-toxicity
#20
Wojciech Bobela, Sameer Nazeeruddin, Graham Knott, Patrick Aebischer, Bernard L Schneider
BACKGROUND: Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson's disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration. METHODS: Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo. RESULTS: Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons...
November 3, 2017: Molecular Neurodegeneration
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