scholarly journals ER stress modulates cellular metabolism

2011 ◽  
Vol 435 (1) ◽  
pp. 285-296 ◽  
Author(s):  
Xiaoli Wang ◽  
Colins O. Eno ◽  
Brian J. Altman ◽  
Yanglong Zhu ◽  
Guoping Zhao ◽  
...  
Keyword(s):  
Er Stress ◽  
Glucose Transporter ◽  
Critical Role ◽  
Lactate Production ◽  
Cellular Metabolism ◽  
Metabolic Effects ◽  
Metabolic Processes ◽  
Glucose Transporter 1 ◽  
Haemopoietic Cells ◽  
Dying Cells

Changes in metabolic processes play a critical role in the survival or death of cells subjected to various stresses. In the present study, we have investigated the effects of ER (endoplasmic reticulum) stress on cellular metabolism. A major difficulty in studying metabolic responses to ER stress is that ER stress normally leads to apoptosis and metabolic changes observed in dying cells may be misleading. Therefore we have used IL-3 (interleukin 3)-dependent Bak−/−Bax−/− haemopoietic cells which do not die in the presence of the ER-stress-inducing drug tunicamycin. Tunicamycin-treated Bak−/−Bax−/− cells remain viable, but cease growth, arresting in G1-phase and undergoing autophagy in the absence of apoptosis. In these cells, we used NMR-based SIRM (stable isotope-resolved metabolomics) to determine the metabolic effects of tunicamycin. Glucose was found to be the major carbon source for energy production and anabolic metabolism. Following tunicamycin exposure, glucose uptake and lactate production are greatly reduced. Decreased 13C labelling in several cellular metabolites suggests that mitochondrial function in cells undergoing ER stress is compromised. Consistent with this, mitochondrial membrane potential, oxygen consumption and cellular ATP levels are much lower compared with untreated cells. Importantly, the effects of tunicamycin on cellular metabolic processes may be related to a reduction in cell-surface GLUT1 (glucose transporter 1) levels which, in turn, may reflect decreased Akt signalling. These results suggest that ER stress exerts profound effects on several central metabolic processes which may help to explain cell death arising from ER stress in normal cells.

scholarly journals Adiponectin regulates glycogen metabolism at the human fetal–maternal interface

2018 ◽  
Vol 61 (3) ◽  
pp. 139-152 ◽  
Author(s):  
Fabien Duval ◽  
Esther Dos Santos ◽  
Benoît Maury ◽  
Valérie Serazin ◽  
Khadija Fathallah ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
Critical Role ◽  
Glycogen Metabolism ◽  
First Trimester ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Glycogen Accumulation ◽  
First Trimester Of Pregnancy

Throughout the entire first trimester of pregnancy, fetal growth is sustained by endometrial secretions, i.e. histiotrophic nutrition. Endometrial stromal cells (EnSCs) accumulate and secrete a variety of nutritive molecules that are absorbed by trophoblastic cells and transmitted to the fetus. Glycogen appears to have a critical role in the early stages of fetal development, since infertile women have low endometrial glycogen levels. However, the molecular mechanisms underlying glycogen metabolism and trafficking at the fetal–maternal interface have not yet been characterized. Among the various factors acting at the fetal–maternal interface, we focused on adiponectin – an adipocyte-secreted cytokine involved in the control of carbohydrate and lipid homeostasis. Our results clearly demonstrated that adiponectin controls glycogen metabolism in EnSCs by (i) increasing glucose transporter 1 expression, (ii) inhibiting glucose catabolism via a decrease in lactate and ATP productions, (iii) increasing glycogen synthesis, (iv) promoting glycogen accumulation via phosphoinositide-3 kinase activation and (v) enhancing glycogen secretion. Furthermore, our results revealed that adiponectin significantly limits glycogen endocytosis by human villous trophoblasts. Lastly, we demonstrated that once glycogen has been endocytosed into placental cells, it is degraded into glucose molecules in lysosomes. Taken as a whole, the present results demonstrate that adiponectin exerts a dual role at the fetal–maternal interface by promoting glycogen synthesis in the endometrium and conversely reducing trophoblastic glycogen uptake. We conclude that adiponectin may be involved in feeding the conceptus during the first trimester of pregnancy by controlling glycogen metabolism in both the uterus and the placenta.

scholarly journals Up-regulation of key glycolysis proteins in cancer development

2018 ◽  
Vol 13 (1) ◽  
pp. 569-581
Author(s):  
Nicole Nowak ◽  
Anna Kulma ◽  
Jan Gutowicz
Keyword(s):  
Cancer Cells ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Cancer Development ◽  
Glucose Transporter 1 ◽  
Expression Of Genes ◽  
Glycolysis Pathway ◽  
Cancer Cell Survival ◽  
Glycolytic Rate

AbstractIn rapid proliferating cancer cells, there is a need for fast ATP and lactate production, therefore cancer cells turn off oxidative phosphorylation and turn on the so called "Warburg effect". This regulating the expression of genes involved in glycolysis. According to many studies, glucose transporter 1, which supplies glucose to the cell, is the most abundantly expressed transporter in cancer cells. Hexokinase 2, is one of four hexokinase isoenzymes, is also another highly expressed enzyme in cancer cells and it functions to enhance the glycolytic rate. The up-regulation of these two proteins has been established as an important factor in promoting development and metastasis in many types of cancer. Furthermore, other enzymes involved in glycolysis pathway such as phosphoglucose isomerase and glyceraldehyde 3-phosphate dehydrogenase, exhibit additional functions in promoting tumor growth in a non-glycolytic way. This review demonstrates the pivotal role of GLUT1, HK2, PGI and GAPDH in cancer development. In particular, we look at how the multifunctional proteins, PGI and GAPDH, affect cancer cell survival. We also present various clinical cancer cases in terms of the overexpression of selected proteins, which may be considered as a therapeutic target.

scholarly journals Regulation of lactate production and glucose transport as well as of glucose transporter 1 and lactate dehydrogenase A mRNA levels by basic fibroblast growth factor in rat Sertoli cells

2002 ◽  
Vol 173 (2) ◽  
pp. 335-343 ◽  
Author(s):  
MF Riera ◽  
SB Meroni ◽  
HF Schteingart ◽  
EH Pellizzari ◽  
SB Cigorraga
Keyword(s):  
Growth Factor ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Short Term ◽  
Glucose Transporter 1 ◽  
Ldh Activity

By using cultured rat Sertoli cells as a model, both the action of basic fibroblast growth factor (bFGF) on lactate production and the site of this action were studied. bFGF stimulated Sertoli cell lactate production in a dose-dependent manner (basal: 7.3+/-0.5; 0.1 ng/ml bFGF: 7.5+/-0.5; 1 ng/ml bFGF: 7.5+/-0.6; 10 ng/ml bFGF: 10.3+/-1.0; 30 ng/ml bFGF: 15.2+/-1.5; 50 ng/ml bFGF: 15.4+/-1.6 microg/microg DNA). Two major sites for the action of this growth factor were identified. First, bFGF was shown to exert short- and long-term stimulatory effects on glucose transport (basal: 1170+/-102; 30 ng/ml bFGF for 120 min: 1718+/-152 and basal: 718+/-64; 30 ng/ml bFGF for 48 h: 1069+/-69 d.p.m./microg DNA respectively). Short-term bFGF stimulation of glucose transport was not inhibited by the protein synthesis inhibitor cycloheximide. These results indicate that short-term bFGF stimulation of glucose uptake does not involve an increase in the number of glucose transporters. On the other hand, stimulation with bFGF for periods of time longer than 12 h increased glucose transporter 1 (GLUT1) mRNA levels. These increased mRNA levels were probably ultimately responsible for the increments in glucose uptake that are observed in long-term treated cultures. Secondly, bFGF increased lactate dehydrogenase (LDH) activity (basal: 31.0+/-1.4; 30 ng/ml bFGF: 45.7+/- 2.4 mIU/microg DNA). The principal subunit component of those LDH isozymes that favors the transformation of pyruvate to lactate is subunit A. bFGF increased LDH A mRNA levels in a dose- and time-dependent manner. In summary, the results presented herein show that glucose transport, LDH activity and GLUT1 and LDH A mRNA levels are regulated by bFGF to achieve an increase in lactate production. These observed regulatory actions provide unequivocal evidence of the participation of bFGF in Sertoli cell lactate production which may be related to normal germ cell development.

scholarly journals Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 317 ◽  
Author(s):  
Jessica Ruzzolini ◽  
Silvia Peppicelli ◽  
Francesca Bianchini ◽  
Elena Andreucci ◽  
Silvia Urciuoli ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Monocarboxylate Transporter ◽  
Metabolic Effects ◽  
Olive Leaf ◽  
Glucose Transporter 1 ◽  
Olive Leaf Extract ◽  
Scientific Attention ◽  
Tumor Types

Oleuropein (Ole), the main bioactive phenolic component of Olea europaea L. has recently attracted the scientific attention for its several beneficial properties, including its anticancer effects. This study is intended to investigate whether an olive leaf extract enriched in Ole (OLEO) may counteract the aerobic glycolysis exploited by tumor cells. We found that OLEO decreased melanoma cell proliferation and motility. OLEO was also able to reduce the rate of glycolysis of human melanoma cells without affecting oxidative phosphorylation. This reduction was associated with a significant decrease of glucose transporter-1, protein kinase isoform M2 and monocarboxylate transporter-4 expression, possible drivers of such glycolysis inhibition. Extending the study to other tumor histotypes, we observed that the metabolic effects of OLEO are not confined to melanoma, but also confirmed in colon carcinoma, breast cancer and chronic myeloid leukemia. In conclusion, OLEO represents a natural product effective in reducing the glycolytic metabolism of different tumor types, revealing an extended metabolic inhibitory activity that may be well suited in a complementary anti-cancer therapy.

Influence of glucose metabolism on vascular smooth muscle cell proliferation

VASA ◽  
2013 ◽  
Vol 42 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Mario Chiong ◽  
Pablo E. Morales ◽  
Gloria Torres ◽  
Tomás Gutiérrez ◽  
Lorena García ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Glucose Metabolism ◽  
Vascular Smooth Muscle ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Critical Role ◽  
Small Gtpase ◽  
Mitofusin 2 ◽  
Glucose Transporter 1 ◽  
Vsmc Proliferation

Differentiation of vascular smooth muscle cells (VSMC) is an essential process of vascular development. VSMC have biosynthetic, proliferative, and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMC play a critical role in the pathogenesis of atherosclerosis and intimal hyperplasia, as well as in a variety of other human diseases, including hypertension, asthma, atherosclerosis and vascular aneurysm. This review provides an overview of the current state of knowledge of molecular mechanisms involved in controlling VSMC proliferation, with particular focus on glucose metabolism and its relationship with mitochondrial bioenergetics. Increased levels of glucose transporter 1 (GLUT1) are observed in VSMC after endothelial injury, suggesting a relationship between glucose uptake and VSMC proliferation. Mitochondrial dysfunction is a common feature in VSMC during atherosclerosis. Alterations in mitochondrial function can be produced by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion. Moreover, exacerbated proliferation was observed in VSMC from pulmonary arteries with hyperpolarized mitochondria and enhanced glycolysis/glucose oxidation ratio. Several lines of evidence highlight the relevance of glucose metabolism in the control of VSMC proliferation, indicating a new area to be explored in the control of vascular pathogenesis.

BPIFB1 Inhibits Vasculogenic Mimicry Via Downregulation Of GLUT1-Mediated H3K27 Acetylation In Nasopharyngeal Carcinoma

2021 ◽  
Author(s):  
Xianjie Jiang ◽  
Xiangying Deng ◽  
Jie Wang ◽  
Yongzhen Mo ◽  
Lei Shi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Glucose Transporter ◽  
Southern China ◽  
Vasculogenic Mimicry ◽  
Ectopic Expression ◽  
Lactate Production ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Glucose Transporter 1

Abstract BackgroundNasopharyngeal carcinoma (NPC) exhibits significant regional differences and a high incidence in Southeast Asia and southern China. Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. Accumulating evidence indicates that BPIFB1 is substantially downregulated in NPC and low BPIFB1 is associated with NPC patient’s poor prognosis. However, the clear molecular mechanism by which BPIFB1 regulates NPC is not well understood.MethodsThe expression of BPIFB1 was analyzed by immunohistochemistry(IHC) and the vasculogenic mimicry was examined by CD31/PAS double staining in NPC clinical samples. The regulation of BPIFB1 on vasculogenic mimicry in vitro and in vivo were performed by tube formation assay and xenograft assay respectively. ECAR was analyzed by Seahorse XF analyzer. 2-NBDG uptake was detected by FACS. Glucose consumption and lactate production were analyzed by Automatic Biochemical Analyzer. Downstream targets of BPIFB1 were validated by western blot, qPCR, Chip-qRT-PCR and dual luciferase reporter assay. Lastly, immunohistochemistry(IHC) was performed to confirm the relationship between BPIFB1 and related genes in NPC clinical samples. ResultsIn this study, we show that BPIFB1 plays an important role in regulating vasculogenic mimicry. Ectopic expression of BPIFB1 significantly inhibits vasculogenic mimicry. Mechanistically, we show that BPIFB1 can inhibits JNK/AP1 signaling which leads to inhibition of glucose transporter 1 (GLUT1) transcription and glycolysis, consequently, resulting in reducing histone H3K27 acetylation and decreasing the expression of vasculogenic mimicry-related VEGFA, VE-cadherin, and MMP2. ConclusionThis study demonstrates that BPIFB1 has a novel biological function in inhibiting glycolysis and vasculogenic mimicry and highlights that BPIFB1 is a potential target for NPC diagnosis and treatment.

scholarly journals Cancer Cells’ Metabolism Dynamics in Renal Cell Carcinoma Patients’ Outcome: Influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1733
Author(s):  
Mariana Morais ◽  
Francisca Dias ◽  
Inês Nogueira ◽  
Anabela Leão ◽  
Nuno Gonçalves ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Glucose Transporter ◽  
Lactate Production ◽  
High Risk Group ◽  
Mrna Levels ◽  
Glucose Transporter 1 ◽  
Glut 1

The cancer cells’ metabolism is altered due to deregulation of key proteins, including glucose transporter 1 (GLUT-1), whose mRNA levels are influenced by microRNAs (miRNAs). Renal cell carcinoma (RCC) is the most common and lethal neoplasia in the adult kidney, mostly due to the lack of accurate diagnosis and follow-up biomarkers. Being a metabolic associated cancer, this study aimed to understand the hsa-miR-144-5p and hsa-miR-186-3p’s potential as biomarkers of clear cell RCC (ccRCC), establishing their role in its glycolysis status. Using three ccRCC lines, the intra- and extracellular levels of both miRNAs, GLUT-1’s mRNA expression and protein levels were assessed. Glucose consumption and lactate production were evaluated as glycolysis markers. A decrease of intracellular levels of these miRNAs and increase of their excretion was observed, associated with an increase of GLUT-1’s levels and glycolysis’ markers. Through a liquid biopsy approach, we found that RCC patients present higher plasmatic levels of hsa-miR-186-3p than healthy individuals. The Hsa-miR144-5p’s higher levels were associated with early clinical stages. When patients were stratified according to miRNAs plasmatic levels, low plasmatic levels of hsa-miR-144-5p and high plasmatic levels of hsa-miR-186-3p (high-risk group) showed the worst overall survival. Thus, circulating levels of these miRNAs may be potential biomarkers of ccRCC prognosis.

scholarly journals Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2783-2792 ◽  
Author(s):  
Hyun Sik Jun ◽  
Young Mok Lee ◽  
Yuk Yin Cheung ◽  
David H. McDermott ◽  
Philip M. Murphy ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nadph Oxidase ◽  
Energy Homeostasis ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Annexin V ◽  
Glucose Transporter 1 ◽  
Atp Production ◽  
Neutrophil Dysfunction

Abstract G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-β (G6Pase-β or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-β in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-β–generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/G6P in neutrophils. Accordingly, a G6Pase-β deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5′-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V–depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3−/− mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3−/− neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-β is essential for normal energy homeostasis. A G6Pase-β deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction.

scholarly journals Hyperglycemia-induced accumulation of advanced glycosylation end products in fibroblast-like synoviocytes promotes knee osteoarthritis

2021 ◽  
Author(s):  
Qingxian Li ◽  
Yinxian Wen ◽  
Linlong Wang ◽  
Biao Chen ◽  
Jun Chen ◽  
...  
Keyword(s):  
High Glucose ◽  
Glucose Transporter ◽  
Critical Role ◽  
Inflammatory Factors ◽  
Glucose Transporter 1 ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation ◽  
Fibroblast Like Synoviocytes

AbstractOsteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.

scholarly journals Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant A549/DDP Cells via the AKT-mTOR-c-Myc Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ye Sun ◽  
Yushi Chen ◽  
Ming Xu ◽  
Chunying Liu ◽  
Hai Shang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pyruvate Kinase ◽  
Glucose Transporter ◽  
A549 Cells ◽  
Lactate Production ◽  
Glycolytic Enzymes ◽  
Glucose Transporter 1 ◽  
Shenmai Injection ◽  
Expression Levels ◽  
Chemotherapy Drugs

Tumor cells, especially drug-resistant cells, predominately support growth by glycolysis even under the condition of adequate oxygen, which is known as the Warburg effect. Glucose metabolism reprogramming is one of the main factors causing tumor resistance. Previous studies on Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of tumors in combination with chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with cisplatin on cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that cisplatin-resistant A549/DDP cells exhibited increased glucose consumption, lactate production, and expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M1/2 (PKM1/2), pyruvate kinase M2 (PKM2), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA), compared with cisplatin-sensitive A549 cells. SMI combined with cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic enzymes, such as HK2, PKM1/2, GLUT1, and pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p-Akt, p-mTOR, and c-Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of cisplatin via glucose metabolism reprogramming. Therefore, the combination of SMI and cisplatin may be a potential therapeutic strategy to treat cisplatin-resistant nonsmall cell lung cancer.

Sign in / Sign up

Export Citation Format

Share Document