University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage.

Rosa, SC, Gonçalves, J, Judas, F, Mobasheri, A, Lopes, C and Mendes, AF (2009) Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage. Arthritis Res Ther, 11 (3).

[img]
Preview
Text
Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage..pdf - ["content_typename_Published version (Publisher's proof or final PDF)" not defined]
Available under License : See the attached licence file.

Download (1MB) | Preview
[img]
Preview
PDF (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview

Abstract

INTRODUCTION: Disorders that affect glucose metabolism, namely diabetes mellitus (DM), may favor the development and/or progression of osteoarthritis (OA). Thus far, little is known regarding the ability of chondrocytes to adjust to variations in the extracellular glucose concentration, resulting from hypoglycemia and hyperglycemia episodes, and so, to avoid deleterious effects resulting from deprivation or intracellular accumulation of glucose. The aim of this study was to compare the ability of normal and OA chondrocytes to regulate their glucose transport capacity in conditions of insufficient or excessive extracellular glucose and to identify the mechanisms involved and eventual deleterious consequences, namely the production of reactive oxygen species (ROS). METHODS: Chondrocytes, isolated from normal and OA human cartilage, were maintained in high-density monolayer cultures, in media without or with 10 or 30 mM glucose. Glucose transport was measured as the uptake of 2-deoxy-D-glucose (2-DG). Glucose transporter-1 (GLUT-1) mRNA and protein content were evaluated by real-time RT-PCR and western blot, respectively. ROS production was measured with 2',7'-dichlorodihydrofluorescein diacetate. RESULTS: Basal and IL-1beta-induced 2-DG uptake, including the affinity (1.066 +/- 0.284 and 1.49 +/- 0.59 mM) and maximal velocity (0.27 +/- 0.08 and 0.33 +/- 0.08 nmol/microg protein/hour), and GLUT-1 content were identical in normal and OA chondrocytes. Glucose deprivation increased 2-DG uptake and GLUT-1 protein both in normal and OA chondrocytes. Exposure to high glucose (30 mM) for 18 or 48 hours decreased those parameters in normal but not in OA chondrocytes. GLUT-1 mRNA levels were unaffected by high glucose, either in normal or OA chondrocytes. The high glucose-induced reduction in GLUT-1 protein in normal chondrocytes was reversed by treatment with a lysosome inhibitor. High glucose induced ROS production, which lasted significantly longer in OA than in normal chondrocytes. CONCLUSIONS: Normal human chondrocytes adjust to variations in the extracellular glucose concentration by modulating GLUT-1 synthesis and degradation which involves the lysosome pathway. Although capable of adjusting to glucose deprivation, OA chondrocytes exposed to high glucose were unable downregulate GLUT-1, accumulating more glucose and producing more ROS. Impaired GLUT-1 downregulation may constitute an important pathogenic mechanism by which conditions characterized by hyperglycemia, like DM, can promote degenerative changes in chondrocytes that can facilitate the progression of OA.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Rosa, SCUNSPECIFIEDUNSPECIFIED
Gonçalves, JUNSPECIFIEDUNSPECIFIED
Judas, FUNSPECIFIEDUNSPECIFIED
Mobasheri, AUNSPECIFIEDUNSPECIFIED
Lopes, CUNSPECIFIEDUNSPECIFIED
Mendes, AFUNSPECIFIEDUNSPECIFIED
Date : 2 June 2009
Identification Number : 10.1186/ar2713
Uncontrolled Keywords : Adult, Aged, Cartilage, Articular, Cells, Cultured, Chondrocytes, Glucose, Glucose Transporter Type 1, Humans, Middle Aged, Osteoarthritis, Oxidative Stress
Related URLs :
Additional Information : © 2009 Rosa et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Depositing User : Symplectic Elements
Date Deposited : 07 Oct 2015 17:57
Last Modified : 07 Oct 2015 17:57
URI: http://epubs.surrey.ac.uk/id/eprint/808685

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800