Vitamin C enters mitochondria via facilitative glucose transporter 1 (Gluti) and confers mitochondrial protection against oxidative injury

2005 ◽  
Vol 19 (12) ◽  
pp. 1657-1667 ◽  
Author(s):  
Sagun KC ◽  
Juan M. Càrcamo ◽  
David W. Golde
Keyword(s):  
Vitamin C ◽  
Glucose Transporter ◽  
Oxidative Injury ◽  
Glucose Transporter 1 ◽  
Facilitative Glucose Transporter

scholarly journals Glut-1 explains the evolutionary advantage of the loss of endogenous vitamin C-synthesis

2019 ◽  
Vol 2019 (1) ◽  
pp. 221-231
Author(s):  
Tabea C Hornung ◽  
Hans-Konrad Biesalski
Keyword(s):  
Vitamin C ◽  
Glucose Transporter ◽  
Dietary Vitamin ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Micronutrient Uptake ◽  
Evolutionary Advantage ◽  
Extracellular Substances ◽  
Human Rbcs

Abstract Introduction During evolution, some species including humans, monkeys and fruit bats lost the ability for ascorbic acid (AA) biosynthesis due to inactivation of the enzyme l-gulono-lactone oxidase (GLO) and subsequently became dependent on dietary vitamin C. There are four current hypotheses in relation to the benefit of vitamin C dependence in the context of adaptation and reproduction. Here we advance and test a new ‘electron transfer hypothesis’, which focusses on the role of the expression of glucose transporter 1 (Glut-1) in red blood cells (RBCs) in recycling vitamin C, thereby increasing the efficiency of micronutrient uptake. Methods To evaluate the benefit of Glut-1 expression, we determined vitamin C uptake into RBCs and potential release from two different species, humans with l-Gulono-lactone-oxidase (GLO-loss) and pigs with functional GLO. Results The oxidized form of vitamin C (dehydroascorbate, DHA) was transported into human RBCs via Glut-1. There was no transport of either the reduced (AA) or the oxidized vitamin in pig erythrocytes. Conclusion We propose that the transport of vitamin C increases an intracellular electron pool, which transfers electrons from intracellular ascorbate to extracellular substances like ascorbyl free radical or DHA, resulting in 100-fold smaller daily requirement of this essential redox sensitive micronutrient. This would be an advantage during seasonal changes of the availability from food and may be the key for the survival of individuals without vitamin C biosynthesis. Lay Summary 40 million years ago some individuals lost the ability to synthesize vitamin C. Why did they survive such as humans until now? Individuals with a specific glucose transporter Glut-1 on their erythrocytes which transports vitamin C need less and are protected from scarcity due to seasons and food competitors.

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth

2000 ◽  
Vol 154 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Yoshikazu Noguchi ◽  
Aya Saito ◽  
Yohei Miyagi ◽  
Shoji Yamanaka ◽  
Doulet Marat ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Glucose Transporter ◽  
Glucose Transporter 1 ◽  
Facilitative Glucose Transporter

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras

2000 ◽  
Vol 154 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Yoshikazu Noguchi ◽  
Takahide Okamoto ◽  
Doulet Marat ◽  
Takaki Yoshikawa ◽  
Aya Saitoh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Glucose Transporter ◽  
Glucose Transporter 1 ◽  
Facilitative Glucose Transporter

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

2018 ◽  
Vol 19 (1) ◽  
pp. 26-40 ◽  
Author(s):  
A.P. Alves ◽  
A.C. Mamede ◽  
M.G. Alves ◽  
P.F. Oliveira ◽  
S.M. Rocha ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Glucose Transporter ◽  
Public Health Problem ◽  
High Morbidity ◽  
Curative Intent ◽  
Malignant Liver Tumor ◽  
Glucose Transporter 1 ◽  
Inhibition Of Glycolysis

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

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