High glucose levels induce inhibition of Na,K-ATPase via stimulation of aldose reductase, formation of microtubules and formation of an acetylated tubulin/Na,K-ATPase complex
| Autor: | Juan F. Rivelli, Gabriela Previtali, Noelia E. Monesterolo, Carlos A. Arce, Cesar H. Casale, Marina R. Amaiden, Adriana C. Fernandez, Verónica S. Santander |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male ATPase Immunoblotting Microtubules Biochemistry Aldehyde Reductase Tubulin Microtubule Cell Line Tumor Chlorocebus aethiops Diabetes Mellitus Animals Humans Sorbitol Rats Wistar Na+/K+-ATPase Aldose reductase Microscopy Confocal Dose-Response Relationship Drug biology Erythrocyte Membrane ATPase complex Glucose transporter Brain Acetylation Cell Biology Middle Aged Molecular biology Rats Glucose COS Cells biology.protein Female Sodium-Potassium-Exchanging ATPase Protein Binding |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 44:1203-1213 |
| ISSN: | 1357-2725 |
| Popis: | Our previous studies demonstrated that acetylated tubulin forms a complex with Na + ,K + -ATPase and thereby inhibits its enzyme activity in cultured COS and CAD cells. The enzyme activity was restored by treatment of cells with l -glutamate, which caused dissociation of the acetylated tubulin/Na + ,K + -ATPase complex. Addition of glucose, but not elimination of glutamate, led to re-formation of the complex and inhibition of the Na + ,K + -ATPase activity. The purpose of the present study was to elucidate the mechanism underlying this effect of glucose. We found that exposure of cells to high glucose concentrations induced: (a) microtubule formation; (b) activation of aldose reductase by the microtubules; (c) association of tubulin with membrane; (d) formation of the acetylated tubulin/Na + ,K + -ATPase complex and consequent inhibition of enzyme activity. Exposure of cells to sorbitol caused similar effects. Studies on erythrocytes from diabetic patients and on tissues containing insulin-insensitive glucose transporters gave similar results. Na + ,K + -ATPase activity was >50% lower and membrane-associated tubulin content was >200% higher in erythrocyte membranes from diabetic patients as compared with normal subjects. Immunoprecipitation analysis showed that acetylated tubulin was a constituent of a complex with Na + ,K + -ATPase in erythrocyte membranes from diabetic patients. Based on these findings, we propose a mechanism whereby glucose triggers a synergistic effect of tubulin and sorbitol, leading to activation of aldose reductase, microtubule formation, and consequent Na + ,K + -ATPase inhibition. |
| Databáze: | OpenAIRE |
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