Monesterolo Noelia E, Nigra Ayelen D, Campetelli Alexis N, Santander Verónica S, Rivelli Juan F, Arce Carlos A, Casale Cesar H
Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Río Cuarto, 5800 Córdoba, Argentina.
Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Biochim Biophys Acta. 2015 Nov;1848(11 Pt A):2813-20. doi: 10.1016/j.bbamem.2015.08.011. Epub 2015 Aug 22.
Our previous studies demonstrated formation of a complex between acetylated tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the lipid environment on structure of this complex and on PMCA activity. Deformability of erythrocytes from hypertensive human subjects was reduced by an increase in membrane tubulin content. In the present study, we examined the regulation of PMCA activity by tubulin in normotensive and hypertensive erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings were that: (i) PMCA was associated with tubulin in normotensive and hypertensive erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte deformability, and (iii) when tubulin was present in the erythrocyte membrane, treatment with DAG or PA led to increased deformability and associated PMCA activity. Taken together, our findings indicate that PMCA activity is involved in deformability of both normotensive and hypertensive erythrocytes. This rheological property of erythrocytes is affected by acetylated tubulin and its lipid environment because both regulate PMCA activity.
我们之前的研究表明,乙酰化微管蛋白与脑质膜Ca(2+)-ATP酶(PMCA)之间会形成一种复合物,以及脂质环境对该复合物结构和PMCA活性的影响。高血压患者红细胞的变形能力会因膜微管蛋白含量增加而降低。在本研究中,我们检测了微管蛋白对正常血压和高血压红细胞中PMCA活性的调节作用,以及外源性添加二酰基甘油(DAG)和磷脂酸(PA)对红细胞变形能力的影响。一些关键发现如下:(i)正常血压和高血压红细胞中的PMCA均与微管蛋白相关;(ii)PMCA酶活性与红细胞变形能力直接相关;(iii)当红细胞膜中存在微管蛋白时,用DAG或PA处理会导致变形能力和相关的PMCA活性增加。综上所述,我们的研究结果表明,PMCA活性与正常血压和高血压红细胞的变形能力均有关。红细胞的这种流变学特性受乙酰化微管蛋白及其脂质环境的影响,因为二者均调节PMCA活性。