High glucose-mediated oxidative stress impairs cell migration

Autor: Marinilce Fagundes dos Santos, Alan F. Horwitz, Miguel Vicente-Manzanares, Marcelo Lazzaron Lamers, Maira Estanislau Soares De Almeida
Přispěvatelé: UAM. Departamento de Medicina
Jazyk: angličtina
Rok vydání: 2011
Předmět:
rac1 GTP-Binding Protein
Anatomy and Physiology
lcsh:Medicine
antioxidant activity
Dermatologic Pathology
medicine.disease_cause
Mice
0302 clinical medicine
Cell Movement
Molecular Cell Biology
Cell polarity
Signaling in Cellular Processes
lcsh:Science
Cells
Cultured
chemistry.chemical_classification
0303 health sciences
Multidisciplinary
Diabetes
Cell Polarity
Cell migration
Adhesion
Patologia
3. Good health
Cell biology
enzyme activity
cell level
030220 oncology & carcinogenesis
diabetes mellitus
Medicine
Cicatrização
Cell Movement Signaling
Research Article
Signal Transduction
Medicina
animal experiment
RAC1
Dermatology
Biology
Cell Line
03 medical and health sciences
Cell Adhesion
medicine
Animals
030304 developmental biology
Reactive oxygen species
lcsh:R
Rats
Oxidative Stress
Glucose
chemistry
Cell culture
NIH 3T3 Cells
lcsh:Q
Reactive Oxygen Species
rhoA GTP-Binding Protein
Wound healing
Oxidative stress
Zdroj: Biblos-e Archivo. Repositorio Institucional de la UAM
instname
PLoS ONE
PLoS ONE, Vol 6, Iss 8, p e22865 (2011)
Repositório Institucional da UFRGS
Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
DOI: 10.1371/journal.pone.0022865
Popis: Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG), 25 mM D-glucose (high glucose, HG) or 25 mM L-glucose medium (osmotic control - OC), we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC). We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients
This study was funded by the following agencies/grants: NIH (GM23244), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (#5181062), Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (06/57508-2), Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (478606/2010-9; 480092/2010-9), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGS (0903698)
Databáze: OpenAIRE
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