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

The International Journal of Biochemistry & Cell Biology
Juan F RivelliCésar H Casale

Abstract

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. Immunop...Continue Reading

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Citations

Mar 1, 2016·The International Journal of Biochemistry & Cell Biology·Ayelén D NigraVerónica S Santander
Jun 21, 2014·Cell Biochemistry and Function·Nicéia Spanholi CalgarotoMaria Rosa Chitolina Schetinger
Nov 1, 2018·Journal of Cellular Physiology·Veronica S SantanderCésar H Casale
Sep 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Parker C WilsonBenjamin D Humphreys
Oct 28, 2019·Cellular and Molecular Life Sciences : CMLS·Ayelén D NigraVerónica S Santander
Aug 19, 2017·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Tomasz RusakMarian Tomasiak
Jan 27, 2021·Journal of Clinical Medicine·Hugo OsórioFátima Carneiro
Oct 29, 2020·Memórias do Instituto Oswaldo Cruz·Raúl Argüello-GarcíaJosé Antonio Velázquez-Domínguez
Jun 8, 2021·Journal of Physiology and Biochemistry·Juan F Rivelli AntonelliCésar H Casale

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