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Involvement of membrane tubulin in erythrocyte deformability and blood pressure

Amaiden, Marina R.a; Monesterolo, Noelia E.a; Santander, Verónica S.a; Campetelli, Alexis N.a; Arce, Carlos A.b; Pie, Juanc; Hope, Sandra I.d; Vatta, Marcelo S.d; Casale, Cesar H.a

doi: 10.1097/HJH.0b013e328353b19a
ORIGINAL PAPERS: Pathophysiological aspects
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Objective: To test the hypothesis that erythrocyte deformability is influenced by changes in the content of membrane tubulin (Mem-tub).

Methods and results: Human erythrocytes contain tubulin distributed in three pools (membrane, sedimentable, soluble). Erythrocytes from hypertensive humans have a higher proportion of Mem-tub. Increased Mem-tub content in hypertensive patients was correlated with decreased erythrocyte deformability. Treatment of erythrocytes from normotensive individuals with taxol increased Mem-tub content and reduced deformability, whereas treatment of hypertensive patients erythrocytes with nocodazole had the opposite effect. In-vivo experiments with rats were performed to examine the possible relationship between Mem-tub content, erythrocyte deformability, and blood pressure. Spontaneously hypertensive rats (SHRs) showed lower erythrocyte deformability than normotensive Wistar rats. During the development of hypertension in SHR, tubulin in erythrocytes is translocated to the membrane, and this process is correlated with decreased deformability. In-vivo treatment (intraperitoneal injection) of SHR with nocodazole decreased Mem-tub content, increased erythrocyte deformability, and decreased blood pressure, whereas treatment of Wistar rats with taxol had the opposite effects.

Conclusion: These findings indicate that increased Mem-tub content contributes to reduced erythrocyte deformability in hypertensive animals.

aDepartamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Río Cuarto

bDepartamento de Química Biológica, Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Facultad de Ciencias Químicas, UNC-CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina

cLaboratorio de Genética Clínica y Funcionalidad Genética, Departamento de Farmacología y Fisiología, Escuela de Medicina, Universidad de Zaragoza, Saragossa, Spain

dCátedra de Fisiología e Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

Correspondence to César H. Casale, Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Rio Cuarto 5800-Córdoba, Argentina. Tel: +54 358 4676422; fax: +54 358 4676232; e-mail: ccasale@exa.unrc.edu.ar

Abbreviations: BSA, bovine serum albumin; Mem-tub, tubulin from membrane fraction; PAGE, polyacrylamide gel electrophoresis; PMSF, phenylmethyl-sulfonyl-fluoride; SDS, sodium dodecyl sulfate; SHR, spontaneously hypertensive rats

Received 19 September, 2011

Revised 2 February, 2012

Accepted 14 March, 2012

© 2012 Lippincott Williams & Wilkins, Inc.