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https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#1
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28643888/combination-of-citrus-polymethoxyflavones-green-tea-polyphenols-and-lychee-extracts-suppresses-obesity-and-hepatic-steatosis-in-high-fat-diet-induced-obese-mice
#2
Min-Hsiung Pan, Guliang Yang, Shiming Li, Ming-Yi Li, Mei-Ling Tsai, Jia-Ching Wu, Vladimir Badmaev, Chi-Tang Ho, Ching-Shu Lai
SCOPE: SlimTrym(®) is a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract and lychee extract. We investigated the effect of dietary SlimTrym(®) on diet-induced obesity and associated non-alcoholic fatty liver disease (NAFLD) in mice. METHODS AND RESULTS: Male C57BL/6 mice were fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym(®) for sixteen weeks. Dietary SlimTrym(®) significantly reduced weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight as well as the size of adipocyte in HFD-fed mice...
June 23, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28643197/ampk-is-activated-early-in-cerebellar-granule-cells-undergoing-apoptosis-and-influences-vadc1-phosphorylation-status-and-activity
#3
A Bobba, E Casalino, G Amadoro, V A Petragallo, A Atlante
The neurodegeneration of cerebellar granule cells, after low potassium induced apoptosis, is known to be temporally divided into an early and a late phase. Voltage-dependent anion channel-1 (VDAC1) protein, changing from the closed inactive state to the active open state, is central to the switch between the early and late phase. It is also known that: (i) VDAC1 can undergo phosphorylation events and (ii) AMP-activated protein kinase (AMPK), the sensor of cellular stress, may have a role in neuronal homeostasis...
June 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#4
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#5
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642089/involvement-of-mapk-akt-gsk-3%C3%AE-and-ampk-mtor-signaling-pathways-in-protection-of-remote-glial-cells-from-axotomy-induced-necrosis-and-apoptosis-in-the-isolated-crayfish-stretch-receptor
#6
E V Berezhnaya, M Y Bibov, M A Komandirov, M A Neginskaya, M V Rudkovskii, A B Uzdensky
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells...
June 19, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#7
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28639909/silencing-of-nrage-induces-autophagy-via-ampk-ulk1-atg13-signaling-pathway-in-nsclc-cells
#8
Yiyang Zhou, Nan Huang, Jianchun Wu, Ni Zhen, Ning Li, Yan Li, Yong-Xin Li
NRAGE has been reported to be overexpressed in cancer cells, especially in lung cancer cells. To determine the role of NRAGE in non-small-cell lung cancer cells, we investigated the effects of NRAGE on autophagy in non-small-cell lung cancer cells. Human A549 and H1299 cells were transfected with NRAGE-specific small-interfering RNA. The Cell Counting Kit-8 and plate clone assay showed that downregulation of NRAGE could induce the proliferation in A549 and H1299 cells. In addition, our data suggested that downregulation of NRAGE enhances autophagosome formation by immunofluorescence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638339/nutritional-and-pharmacological-strategies-to-regulate-microglial-polarization-in-cognitive-aging-and-alzheimer-s-disease
#9
REVIEW
Emiliano Peña-Altamira, Sabrina Petralla, Francesca Massenzio, Marco Virgili, Maria L Bolognesi, Barbara Monti
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28638220/green-tea-polyphenols-ameliorate-non-alcoholic-fatty-liver-disease-through-upregulating-ampk-activation-in-high-fat-fed-zucker-fatty-rats
#10
Yi Tan, Jane Kim, Jing Cheng, Madeleine Ong, Wei-Guo Lao, Xing-Liang Jin, Yi-Guang Lin, Linda Xiao, Xue-Qiong Zhu, Xian-Qin Qu
AIM: To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats. METHODS: Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#11
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636994/a-novel-ampk-activator-hernandezine-inhibits-lps-induced-tnf%C3%AE-production
#12
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/28636830/attenuation-of-hepatic-steatosis-by-purple-sweet-potato-color-is-associated-with-blocking-src-erk-c-ebp%C3%AE-signalling-in-high-fat-diet-treated-mice
#13
Xin Wang, Zi-Feng Zhang, Gui-Hong Zheng, Ai-Min Wang, Chun-Hui Sun, Su-Ping Qin, Juan Zhuang, Jun Lu, Dai-Fu Ma, Yuan-Lin Zheng
Our previous work showed that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into four groups: Control group, HFD group, HFD+PSPC group and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/kg/day. Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice...
June 21, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28634643/acute-high-caffeine-exposure-increases-autophagic-flux-and-reduces-protein-synthesis-in-c2c12-skeletal-myotubes
#14
M A Hughes, R M Downs, G W Webb, C L Crocker, S T Kinsey, Bradley L Baumgarner
Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux...
June 20, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28634570/to-use-or-not-to-use-metformin-in-cerebral-ischemia-a-review-of-the-application-of-metformin-in-stroke-rodents
#15
REVIEW
Isaac Arbeláez-Quintero, Mauricio Palacios
Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28634089/wedelolactone-a-plant-coumarin-prevents-vascular-smooth-muscle-cell-proliferation-and-injury-induced-neointimal-hyperplasia-through-akt-and-ampk-signaling
#16
Lu Peng, Xuefeng Huang, Xin Jin, Zuo Jing, Lichao Yang, Yu Zhou, Jie Ren, Yun Zhao
Wedelolactone (WDL) is a natural compound derived from Chinese herbal medicine Eclipta prostrate L, and has been reported to exhibit various effects potentially beneficial for human health. However, the possible preventive effects of WDL toward vascular remodeling and mechanisms involved have not been investigated to date. In this study, we investigated the effects of WDL on proliferation induced by platelet-derived growth factor (PDGF) in primary rat aortic smooth muscle cells (VSMCs) and on neointimal hyperplasia resulted from balloon injury in rats...
June 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28632947/pimozide-reduces-toxic-forms-of-tau-in-tauc3-mice-via-ampk-mediated-autophagy
#17
YoungDoo Kim, Eun Il Jeong, Jihoon Nah, Seung-Min Yoo, WonJae Lee, Youbin Kim, Seowon Moon, Se-Hoon Hong, Yong-Keun Jung
In neurodegenerative diseases like Alzheimer's disease (AD), tau is hyperphosphorylated and forms aggregates and neurofibrillary tangles in affected neurons. Autophagy is critical to clear the aggregates of disease-associated proteins and is often altered in patients and animal models of AD. Because mTOR (mechanistic target of rapamycin) negatively regulates autophagy and is hyperactive in the brains of patients with AD, mTOR is an attractive therapeutic target for AD. However, pharmacological strategies to increase autophagy by targeting mTOR inhibition cause various side effects...
June 20, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28632780/metformin-intake-associates-with-better-cognitive-function-in-patients-with-huntington-s-disease
#18
David Hervás, Victoria Fornés-Ferrer, Ana Pilar Gómez-Escribano, María Dolores Sequedo, Carmen Peiró, José María Millán, Rafael P Vázquez-Manrique
Huntington's disease (HD) is an inherited, dominant neurodegenerative disorder caused by an abnormal expansion of CAG triplets in the huntingtin gene (htt). Despite extensive efforts to modify the progression of HD thus far only symptomatic treatment is available. Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes associated to HD...
2017: PloS One
https://www.readbyqxmd.com/read/28632765/ctrp3-is-a-novel-biomarker-for-diabetic-retinopathy-and-inhibits-hghl-induced-vcam-1-expression-in-an-ampk-dependent-manner
#19
Zheyi Yan, Jianli Zhao, Lu Gan, Yanqing Zhang, Rui Guo, Xiaoming Cao, Wayne Bond Lau, Xin Ma, Yajing Wang
OBJECTIVES: Diabetic retinopathy (DR) is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs) has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology. DESIGN: The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM) patients diagnosed with DR...
2017: PloS One
https://www.readbyqxmd.com/read/28629357/xuefuzhuyu-decoction-protected-cardiomyocytes-against-hypoxia-reoxygenation-injury-by-inhibiting-autophagy
#20
Xiaowen Shi, Haiyan Zhu, Yuanyuan Zhang, Mingmei Zhou, Danli Tang, Huamin Zhang
BACKGROUND: XuefuZhuyu decoction (XFZY) is a well-known traditional Chinese herbal medicine for the treatment of various cardiovascular diseases, such as unstable angina pectoris and myocardial ischemia-reperfusion injury. However, the mechanism by which XFZY contributes to the amelioration of cardiac injury remains unclear. METHODS: H9C2 cells were cultured under the hypoxic condition for 10 h and reoxygenated for 2 h. In the presence of various concentrations of XFZY for 12 h, the cell viability was measured by MTT assay...
June 19, 2017: BMC Complementary and Alternative Medicine
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