Instituto de Biotecnología Ambiental y Salud (INBIAS), CONICET - UNRC)- Río Cuarto, 5800, Córdoba, Argentina.
Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico- Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina.
J Physiol Biochem. 2023 Aug;79(3):511-527. doi: 10.1007/s13105-023-00946-4. Epub 2023 Feb 11.
In previous research, we observed that tubulin can be found in three fractions within erythrocytes, i.e., attached to the membrane, as a soluble fraction, or as part of a structure that can be sedimented by centrifugation. Given that its differential distribution within these fractions may alter several hemorheological properties, such as erythrocyte deformability, the present work studied how this distribution is in turn affected by Ca, another key player in the regulation of erythrocyte cytoskeleton stability. The effect of Ca on some hemorheological parameters was also assessed. The results showed that when Ca concentrations increased in the cell, whether by the addition of ionophore A23187, by specific plasma membrane CaATPase (PMCA) inhibition, or due to arterial hypertension, tubulin translocate to the membrane, erythrocyte deformability decreased, and phosphatidylserine exposure increased. Moreover, increased Ca was associated with an inverse correlation in the distribution of tubulin and spectrin, another important cytoskeleton protein. Based on these findings, we propose the existence of a mechanism of action through which higher Ca concentrations in erythrocytes trigger the migration of tubulin to the membrane, a phenomenon that results in alterations of rheological and molecular aspects of the membrane itself, as well as of the integrity of the cytoskeleton.
在之前的研究中,我们观察到微管蛋白可以在红细胞中分为三个部分,即附着在膜上、作为可溶性部分,或作为可以通过离心沉淀的结构的一部分。鉴于其在这些部分中的差异分布可能会改变几种血液流变学特性,如红细胞变形性,本研究探讨了这种分布又是如何受到 Ca 的影响的,Ca 是调节红细胞细胞骨架稳定性的另一个关键因素。还评估了 Ca 对一些血液流变学参数的影响。结果表明,当细胞内 Ca 浓度增加时,无论是通过添加离子载体 A23187、特异性质膜 CaATP 酶 (PMCA) 抑制,还是由于动脉高血压,微管蛋白向膜迁移,红细胞变形性降低,磷脂酰丝氨酸暴露增加。此外,增加的 Ca 与微管蛋白和另一种重要的细胞骨架蛋白血影蛋白的分布呈负相关。基于这些发现,我们提出了一种作用机制的存在,即红细胞中较高的 Ca 浓度触发微管蛋白向膜的迁移,这种现象导致膜本身的流变学和分子方面以及细胞骨架的完整性发生改变。