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https://www.readbyqxmd.com/read/28634229/akt-activation-by-ca2-calmodulin-dependent-protein-kinase-kinase-2-camkk2-in-ovarian-cancer-cells
#1
Angela M Gocher, Gissou Azabdaftari, Lindsey M Euscher, Shuhang Dai, Loukia G Karacosta, Thomas F Franke, Arthur M Edelman
Hyperactivation of Akt is associated with oncogenic changes in the growth, survival and chemoresistance of cancer cells. The PI3K/Phosphoinositide-dependent kinase (PDK) 1 pathway represents the canonical mechanism for phosphorylation of Akt at its primary activation site, Thr308. We observed that Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (beta) (CaMKK2) is highly expressed in high-grade serous ovarian cancer and investigated its role in Akt activation in ovarian cancer (OVCa) cell lines (OVCAR-3, SKOV-3, Caov-3)...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28632756/identification-of-atf-7-and-the-insulin-signaling-pathway-in-the-regulation-of-metallothionein-in-c-elegans-suggests-roles-in-aging-and-reactive-oxygen-species
#2
Julie A Hall, Matthew K McElwee, Jonathan H Freedman
It has been proposed that aging results from the lifelong accumulation of intracellular damage via reactions with reactive oxygen species (ROS). Metallothioneins are conserved cysteine-rich proteins that function as efficient ROS scavengers and may affect longevity. To better understand mechanisms controlling metallothionein expression, the regulatory factors and pathways that controlled cadmium-inducible transcription of the C. elegans metallothionein gene, mtl-1, were identified. The transcription factor ATF-7 was identified in both ethylmethanesulfonate mutagenesis and candidate gene screens...
2017: PloS One
https://www.readbyqxmd.com/read/28620312/thermodynamics-in-gliomas-interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma
#3
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28595656/ros-production-induced-by-braf-inhibitor-treatment-rewires-metabolic-processes-affecting-cell-growth-of-melanoma-cells
#4
Giulia Cesi, Geoffroy Walbrecq, Andreas Zimmer, Stephanie Kreis, Claude Haan
BACKGROUND: Most melanoma patients with BRAF(V600E) positive tumors respond well to a combination of BRAF kinase and MEK inhibitors. However, some patients are intrinsically resistant while the majority of patients eventually develop drug resistance to the treatment. For patients insufficiently responding to BRAF and MEK inhibitors, there is an ongoing need for new treatment targets. Cellular metabolism is such a promising new target line: mutant BRAF(V600E) has been shown to affect the metabolism...
June 8, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28574836/hpv-associated-differential-regulation-of-tumor-metabolism-in-oropharyngeal-head-and-neck-cancer
#5
Young-Suk Jung, Abdo J Najy, Wei Huang, Seema Sethi, Michael Snyder, Wael Sakr, Gregory Dyson, Maik Hüttemann, Icksoo Lee, Rouba Ali-Fehmi, Silvia Franceschi, Linda Struijk, Harold E Kim, Ikuko Kato, Hyeong-Reh Choi Kim
HPV-positive oropharyngeal cancer patients experience significantly lower locoregional recurrence and higher overall survival in comparison with HPV-negative patients, especially among those who received radiation therapy. The goal of the present study is to investigate the molecular mechanisms underlying the differential radiation sensitivity between HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Here, we show that HPV-negative HNSCC cells exhibit increased glucose metabolism as evidenced by increased production of lactate, while HPV-positive HNSCC cells effectively utilize mitochondrial respiration as evidenced by increased oxygen consumption...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28556776/hif-1%C3%AE-is-required-for-disturbed-flow-induced-metabolic-reprogramming-in-human-and-porcine-vascular-endothelium
#6
David Wu, Ru-Ting Huang, Robert B Hamanaka, Matthew D Krause, Myung-Jin Oh, Cheng-Hsiang Kuo, Recep Nigdelioglu, Angelo Y Meliton, Leah Witt, Guohao Dai, Mete Civelek, Nanduri R Prabhakar, Yun Fang, Gökhan M Mutlu
Hemodynamic forces regulate vascular functions. Disturbed flow (DF) occurs in arterial bifurcations and curvatures, activates endothelial cells (ECs), and results in vascular inflammation and ultimately atherosclerosis. However, how DF alters EC metabolism, and whether resulting metabolic changes induce EC activation, is unknown. Using transcriptomics and bioenergetic analysis, we discovered that DF induces glycolysis and reduces mitochondrial respiratory capacity in human aortic ECs. DF-induced metabolic reprogramming required hypoxia inducible factor-1α (HIF-1α), downstream of NAD(P)H oxidase-4 (NOX4)-derived reactive oxygen species (ROS)...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28490895/healthcare-resource-consumption-and-cost-of-care-among-patients-with-polycystic-kidney-disease-in-italy
#7
Luca Degli Esposti, Chiara Veronesi, Valentina Perrone, Stefano Buda, Antonio Santoro
OBJECTIVE: The aim of this study was to assess healthcare resource consumption and its associated costs among patients with polycystic kidney disease (PKD) in a real-world setting. METHODS: An observational retrospective cohort analysis was conducted using data from the administrative databases of four Italian local health units. Data for patients who were diagnosed with PKD during the inclusion period (January 1, 2010 to December 31, 2012) were extracted. The date on which a patient's first PKD hospitalization occurred during the inclusion period was defined as the index date (ID), and the ID was defined as the date of the first dialysis treatment recorded during the inclusion period for patients undergoing dialysis...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28484259/the-physiological-and-molecular-response-of-aurelia-sp-1-under-hypoxia
#8
Guoshan Wang, Yu Zhen, Zhigang Yu, Yan Shi, Qing Zhao, Jianyan Wang, Tiezhu Mi
Few studies have been published on the mechanisms of hypoxia response and tolerance in jellyfish, especially with respect to the regulatory mechanism at the molecular level. In this study, Aurelia sp.1, which is frequently found in Chinese coastal waters, was cultivated in a hypoxic system to determine the molecular mechanisms underlying its hypoxic response by studying the physiological activity, gene expression and metabolite contents in the prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) oxygen-sensing system...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423362/trop2-promotes-proliferation-migration-and-metastasis-of-gallbladder-cancer-cells-by-regulating-pi3k-akt-pathway-and-inducing-emt
#9
Xinxing Li, Shifeng Teng, Yanyan Zhang, Weigang Zhang, Xianwen Zhang, Kai Xu, Houshan Yao, Jun Yao, Haolu Wang, Xiaowen Liang, Zhiqian Hu
The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414314/cell-competition-with-normal-epithelial-cells-promotes-apical-extrusion-of-transformed-cells-through-metabolic%C3%A2-changes
#10
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-Ichi Miyazaki, Michael R Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#11
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28395173/particular-phosphorylation-of-pi3k-akt-on-thr308-via-pdk-1-and-pten-mediates-melatonin-s-neuroprotective-activity-after-focal-cerebral-ischemia-in-mice
#12
Ulkan Kilic, Ahmet Burak Caglayan, Mustafa Caglar Beker, Mehmet Yalcin Gunal, Berrak Caglayan, Esra Yalcin, Taha Kelestemur, Reyhan Zeynep Gundogdu, Burak Yulug, Bayram Yılmaz, Bilal Ersen Kerman, Ertugrul Kilic
Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28371849/therapeutic-inhibition-of-mir-375-attenuates-post-mi-inflammatory-response-and-left-ventricular-dysfunction-via-pdk-1-akt-signaling-axis
#13
Venkata Naga Srikanth Garikipati, Suresh Kumar Verma, Darukeshwara Jolardarashi, Zhongjian Cheng, Jessica Ibetti, Maria Cimini, Yan Tang, Mohsin Khan, Yujia Yue, Cindy Benedict, Emily Nickoloff, May M Trungcao, Erhe Gao, Prasanna Krishnamurthy, David A Goukassian, Walter J Koch, Raj Kishore
Aims: Increased miR-375 levels has been implicated in rodent models of myocardial infarction (MI) and with patients with heart failure. However, no prior study had established a therapeutic role of miR-375 in ischemic myocardium. Therefore, we assessed whether inhibition of MI-induced miR-375 by LNA anti-miR -375 can improve recovery after acute MI. Methods and Results: Ten weeks old mice were treated with either control or LNA anti miR-375 after induction of MI by LAD ligation...
March 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28367092/pkd-knockdown-inhibits-pressure-overload-induced-cardiac-hypertrophy-by-promoting-autophagy-via-akt-mtor-pathway
#14
Di Zhao, Wei Wang, Hao Wang, Honghai Peng, Xiangjuan Liu, Weixing Guo, Guohai Su, Zhuo Zhao
Growing evidence shows that protein kinase D (PKD) plays an important role in the development of pressure overload-induced cardiac hypertrophy. However, the mechanisms involved are not clear. This study tested our hypothesis that PKD might mediate cardiac hypertrophy by negatively regulating autophagy using the technique of PKD knockdown by siRNA. Cardiac hypertrophy was induced in 8-week old male C57BL/6 mice by transverse aortic constriction (TAC). TAC mice were then divided into five groups receiving the treatments of vehicle (DMSO), an autophagy inducer rapamycin (1 mg/kg/day, i...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28366735/regulator-of-g-protein-signaling-1-modulates-paraquat-induced-oxidative-stress-and-longevity-via-the-insulin-like-signaling-pathway-in-caenorhabditis-elegans
#15
Mingyu Wu, Xin Kang, Qiang Wang, Chunyu Zhou, Chandra Mohan, Ai Peng
Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of rgs-1 dramatically promoted paraquat resistance in C...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#16
REVIEW
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28238857/asiaticoside-attenuation-of-rotenone-induced-oxidative-burden-in-a-rat-model-of-hemiparkinsonism-by-maintaining-the-phosphoinositide-mediated-synaptic-integrity
#17
Margabandhu Gopi, Vanisree Arambakkam Janardhanam
Asiaticoside (AS), a triterpenoid saponin isolated from the Indian medicinal herb Centella asiatica is known to exert a neuroprotective effect by attenuating the neurobehavioral, neurochemical and pathological changes in animal models. However, its potential neuroprotection in rotenone-induced hemiparkinsonism which implicates phospholipid-mediated neurotransmission remains unclear. Therefore, we have investigated the neuroprotective effects of AS in rat model of ROT-infused hemiparkinsonism with respect to phosphoinositides-assisted cytodynamics and synaptic function...
February 24, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28230160/global-view-of-cognate-kinase-activation-by-the-human-pyruvate-dehydrogenase-complex
#18
Elena L Guevara, Luying Yang, Barbara Birkaya, Jieyu Zhou, Natalia S Nemeria, Mulchand S Patel, Frank Jordan
The human pyruvate dehydrogenase complex (PDC) comprises four multidomain components, E1, E3, E2 and an E3-binding protein (E3BP), the latter two forming the core as E2·E3BP sub-complex. Pyruvate flux through PDC is regulated via phosphorylation (inactivation) at E1 by four PDC kinases (PDKs), and reactivation by two PDC phosphatases. Up-regulation of PDK isoform gene expression is reported in several forms of cancer, while PDKs may be further activated by PDC by binding to the E2·E3BP core. Hence, the PDK: E2·E3BP interaction provides new therapeutic targets...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#19
COMPARATIVE STUDY
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#20
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
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