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Autophagy and GLUT-1

Irene Filippi, Ilaria Saltarella, Carlo Aldinucci, Fabio Carraro, Roberto Ria, Angelo Vacca, Antonella Naldini
BACKGROUND/AIMS: Hypoxia is a powerful stimulator of angiogenesis under physiological as well as pathological conditions. Normal endothelial cells (EC), such as human umbilical vein EC (HUVEC), are relatively affected by hypoxic insult in terms of cell survival. In contrast, EC from tumors are particularly resistant to hypoxia-induced cell death. Previous reports have shown that EC in bone marrow from multiple myeloma (MM) patients had a hypoxic phenotype, even under normoxic conditions...
March 21, 2018: Cellular Physiology and Biochemistry
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
Yu Pan, Xiu Hong Yang, Li Li Guo, Yan Hong Gu, Qing Yan Qiao, Hui Min Jin
Erythropoietin (EPO) can reduce insulin resistance (IR) in adipocytes; however, it is unknown whether EPO can decrease IR in skeletal muscle. Here we investigated whether EPO could reduce IR in type 2 diabetic mouse skeletal muscle and its possible signaling mechanisms of action. Twelve-week-old db/db diabetic mice were employed in this study. Systemic use of EPO improved glucose profiles in type 2 diabetic mice after 4 and 8 weeks treatment. EPO up-regulated EPOR protein expression in skeletal muscle, and subsequently activated downstream signaling molecules such as JAK2, IRS-1, PI3K, AKT, and eNOS...
2017: International Journal of Biological Sciences
Xiu Zhang, Dan Wu, Mohanad Aldarouish, Xiaodong Yin, Chunyan Li, Cailian Wang
Pancreatic cancer is one of the most lethal malignancies of all types of cancer due to lack of early symptoms and its resistance to conventional therapy. In our previous study, we have shown that v‑ets erythroblastosis virus E26 oncogene homolog‑1 (ETS‑1) promote cell migration and invasion in pancreatic cancer cells. However, the function of ETS‑1 in regulation of glycolysis and autophagy during progression of pancreatic cancer has not been defined yet. In this study, we sought to identify the potential role for silencing ETS‑1 in reducing the expression of glucose transporter‑1 (GLUT‑1) to disturb glycolysis through alteration of 'Warburg effect', by which could result in AMP‑activated protein kinase (AMPK) activation, autophagy induction and reduction of cell viability...
January 2017: International Journal of Oncology
Annadurai Anandhan, Shulei Lei, Roman Levytskyy, Aglaia Pappa, Mihalis I Panayiotidis, Ronald L Cerny, Oleh Khalimonchuk, Robert Powers, Rodrigo Franco
While environmental exposures are not the single cause of Parkinson's disease (PD), their interaction with genetic alterations is thought to contribute to neuronal dopaminergic degeneration. However, the mechanisms involved in dopaminergic cell death induced by gene-environment interactions remain unclear. In this work, we have revealed for the first time the role of central carbon metabolism and metabolic dysfunction in dopaminergic cell death induced by the paraquat (PQ)-α-synuclein interaction. The toxicity of PQ in dopaminergic N27 cells was significantly reduced by glucose deprivation, inhibition of hexokinase with 2-deoxy-D-glucose (2-DG), or equimolar substitution of glucose with galactose, which evidenced the contribution of glucose metabolism to PQ-induced cell death...
July 2017: Molecular Neurobiology
Sabrina Engelhardt, Sheng-Fu Huang, Shalmali Patkar, Max Gassmann, Omolara O Ogunshola
BACKGROUND: Undisturbed functioning of the blood-brain barrier (BBB) crucially depends on paracellular signaling between its associated cells; particularly endothelial cells, pericytes and astrocytes. Hypoxic and ischemic injuries are closely associated with disturbed BBB function and the contribution of perivascular cells to hypoxic/ischemic barrier regulation has gained increased attention. Regardless, detailed information on the basal hypoxic/ischemic responses of the barrier-associated cells is rare and the outcome of such cell-specific responses on BBB modulation is not well understood...
2015: Fluids and Barriers of the CNS
Elżbieta Kania, Beata Pająk, Arkadiusz Orzechowski
Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca(2+) homeostasis perturbation and starvation...
2015: BioMed Research International
Zongwei Li, Yingying Wang, Ian P Newton, Lichao Zhang, Pengyu Ji, Zhuoyu Li
Compared with normal differentiated cells, cancer cells take up much more glucose and metabolize it mainly via aerobic glycolysis. This metabolic phenotype is characterized with high expression of glucose transporters (Gluts) and pyruvate kinase M2 (PKM2). Glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently up-regulated in cancer cells, however, whether it is directly implicated in glucose metabolism remains to be elucidated. Here we report that upon glucose deficiency, the induction of GRP78 resulted in enhanced HIF-1α transcription, accompanied by a transient increased expression of Glut-1...
June 2015: Cellular Signalling
Xiaoxi Han, Shengkun Sun, Ming Zhao, Xiang Cheng, Guozhu Chen, Song Lin, Yifu Guan, Xiaodan Yu
Celastrol, a tripterine derived from the traditional Chinese medicine plant Tripterygium wilfordii Hook F. ("Thunder of God Vine"), has been reported to have multiple effects, such as anti-inflammation, suppression of tumor angiogenesis, inhibition of tumor growth, induction of apoptosis and protection of cells against human neurodegenerative diseases. However, the mechanisms that underlie these functions are not well defined. In this study, we reported for the first time that Celastrol could induce HIF-1α protein accumulation in multiple cancer cell lines in an oxygen-independent manner and that the enhanced HIF-1α protein entered the nucleus and promoted the transcription of the HIF-1 target genes VEGF and Glut-1...
2014: PloS One
Yu-I Shen, Hasan E Abaci, Yoni Krupsi, Lien-Chun Weng, Jason A Burdick, Sharon Gerecht
Three-dimensional (3D) tissue culture models may recapitulate aspects of the tumorigenic microenvironment in vivo, enabling the study of cancer progression in vitro. Both hypoxia and matrix stiffness are known to regulate tumor growth. Using a modular culture system employing an acrylated hyaluronic acid (AHA) hydrogel, three hydrogel matrices with distinctive degrees of viscoelasticity - soft (78±16 Pa), medium (309± 57 Pa), and stiff (596± 73 Pa) - were generated using the same concentration of adhesion ligands...
May 1, 2014: Biomaterials Science
Junjeong Choi, Do Hee Kim, Woo Hee Jung, Ja Seung Koo
INTRODUCTION: The aim of this study was to investigate the differential expression of markers related to metabolic, mitochondrial and autophagy status in different molecular subtypes of breast cancer. METHODS: Using tissue microarray sections generated from 740 cases of breast cancer, we performed immunohistochemical staining for Glut-1, CAIX, MCT4, ATP synthase, glutaminase, BNIP3, Beclin-1, LC3A, LC3B and p62. Based on the immunohistochemical expression of estrogen receptor (ER), progesterone (PR), HER2, and Ki-67 labeling index, the cases were classified into luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)...
2013: Breast Cancer Research: BCR
Sewha Kim, Do Hee Kim, Woo-Hee Jung, Ja Seung Koo
The aim of study was to investigate the metabolism of tumor and stromal cells necessary to determine differential tumor-stroma metabolic interactions according to the molecular subtypes of triple-negative breast cancer (TNBC). Tissues from 132 patients of TNBC were prepared for use as tissue microarrays (TMA). Expression of CK5/6, EGFR, claudin 3, claudin 4, claudin7, E-cadherin, AR, GGT1, STAT1, and interleukin-8 was evaluated by immunohistochemical staining using TMA to classify molecular subtypes of TNBC...
June 2013: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Georgia Karpathiou, Efthimios Sivridis, Michael Koukourakis, Dimitrios Mikroulis, Demosthenes Bouros, Marios Froudarakis, George Bougioukas, Efstratios Maltezos, Alexandra Giatromanolaki
We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1...
July 2013: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Kimberley M Mellor, James R Bell, Rebecca H Ritchie, Lea M D Delbridge
Clinical studies in humans strongly support a link between insulin resistance and non-ischaemic heart failure. The occurrence of a specific insulin-resistant cardiomyopathy, independent of vascular abnormalities, is now recognized. The progression of cardiac pathology linked with insulin resistance is poorly understood. Cardiac insulin resistance is characterized by reduced availability of sarcolemmal Glut-4 transporters and consequent lower glucose uptake. A shift away from glycolysis towards fatty acid oxidation for ATP supply is apparent and is associated with myocardial oxidative stress...
January 2013: Clinical and Experimental Pharmacology & Physiology
Belma Turan, Erkan Tuncay, Guy Vassort
Resveratrol, a natural phytoalexin found in wine has the potential to impact a variety of human diseases. Resveratrol like other polyphenols activates many of the same intracellular pathways as those activated by caloric restriction. It can quench reactive oxidative species, ROS and induce eNOS and iNOS expression. Resveratrol also can activate SIRT1, a NAD⁺-dependent deacetylase, that leads an improved in mitochondrial function, and then this procedure turns to activate the transcription factor Nrf2 that coordinates expression of key antioxidant mechanisms by binding to the antioxidant response elements...
April 2012: Journal of Bioenergetics and Biomembranes
Shang-Ming Huang, Shin-Yi Tsai, Jer-An Lin, Chi-Hao Wu, Gow-Chin Yen
SCOPE: This study investigated whether flavonoids, such as hesperetin and hesperidin, inhibited amyloid β (Aβ)-impaired glucose utilization through regulating cellular autophagy in insulin-stimulated neuronal cells. METHODS AND RESULTS: In this study, we used a toxic Aβ1-42 peptide to impair insulin-stimulated glucose utilization in Neuro-2A cells, and this study also hypothesized that Aβ-induced autophagy might be emerging as a key process regulating neuronal glucose uptake...
April 2012: Molecular Nutrition & Food Research
Hasan Erbil Abaci, Rachel Truitt, Eli Luong, German Drazer, Sharon Gerecht
Hypoxia plays an important role in vascular development through hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation and downstream pathway activation. We sought to explore the in vitro response of cultures of human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), human endothelial progenitor cells (hEPCs), and human umbilical cord vein endothelial cells (HUVECs) to normoxic and hypoxic oxygen tensions. We first measured dissolved oxygen (DO) in the media of adherent cultures in atmospheric (21% O(2)), physiological (5% O(2)), and hypoxic oxygen conditions (1% O(2))...
June 2010: American Journal of Physiology. Cell Physiology
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