Alterations of hemorheological parameters and tubulin content in erythrocytes from diabetic subjects |
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| Affiliation: | 2. Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee;3. Department of Medicine (Endocrinology) and Research Service, Veterans Affairs Medical Center, Memphis, Tennessee;4. Department of Preventive Medicine, College of Medicine, Veterans Affairs Medical Center, University of Tennessee Health Science Center, Memphis, Tennessee;2. Department of Epidemiology and Biostatistics, Guangxi Medical University, Nanning, Guangxi, China;3. Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China;4. State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China;5. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;1. Department of Life Science, Hanyang University, Seoul 133-791, Republic of Korea;2. Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea;3. Department of Mechanical Convergence Engineering, Hanyang University, Seoul 133-791, Republic of Korea;4. Institute of Nano Science and Technology, Hanyang University, Seoul 133-791, Republic of Korea;1. Yale School of Medicine, Department of Genetics and Howard Hughes Medical Institute, Boyer Center, 295 Congress Avenue, New Haven, CT 065105, USA;2. Department of Anatomy and Cell Biology, 808 S. Wood St., Rm 578 (M/C 512), University of Illinois at Chicago, Chicago, IL 60612, USA |
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| Abstract: | Treatment of human erythrocytes with high glucose concentrations altered the content and distributions of three tubulin isotypes, with consequent reduction of erythrocyte deformability and osmotic resistance. In erythrocytes from diabetic subjects (D erythrocytes), (i) tubulin in the membrane-associated fraction (Mem-Tub) was increased and tubulin in the sedimentable fraction (Sed-Tub) was decreased, (ii) deformability was lower than in erythrocytes from normal subjects (N erythrocytes), and (iii) detyrosinated/acetylated tubulin content was higher in the Mem-Tub fraction and tyrosinated/acetylated tubulin content was higher in the Sed-Tub fraction, in comparison with N erythrocytes. Similar properties were observed for human N erythrocytes treated with high glucose concentrations, and for erythrocytes from rats with streptozotocin-induced diabetes. In N erythrocytes, high-glucose treatment caused translocation of tubulin from the Sed-Tub to Mem-Tub fraction, thereby reducing deformability and inducing acetylation/tyrosination in the Sed-Tub fraction. The increased tubulin acetylation in these cells resulted from inhibition of deacetylase enzymes. Increased tubulin acetylation and translocation of this acetylated tubulin to the Mem-Tub fraction were both correlated with reduced osmotic resistance. Our findings suggest that (i) high glucose concentrations promote tubulin acetylation and translocation of this tubulin to the membrane, and (ii) this tubulin is involved in regulation of erythrocyte deformability and osmotic fragility. |
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| Keywords: | Tubulin Diabetes Erythrocyte deformability Human erythrocytes Acetylated tubulin Osmotic fragility |
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