Neurotoxic amyloid β-peptide and tau produce cytokine-like effects on PMCA in glioblastoma cell lines, enhancing its activity and isoforms expression.

Abstract

The transformation of astrocytes into neurotoxic reactive astrocytes, classified as A1, by inflammatory cytokines, and their link to brain damage and neurodegenerative diseases has been widely documented. However, the roles of two biomarkers of Alzheimer's disease (AD), amyloid β-peptide (Aβ) and tau, and that of calcium pumps which are involved in the fine-tuning of calcium homeostasis, are poorly understood in astrocytes. In this study, we showed that treating astrocytoma U-251 cells with a cocktail of cytokines significantly increased plasma membrane Ca²⁺-ATPase (PMCA) activity and expression levels of the four PMCA isoforms. Moreover, treatment of cells with Aβ1-42 or tau induced a similar upregulation of PMCA activity and isoform expression levels as cytokines. These effects support the close association of Aβ and tau with inflammation. This study may help better understand the role of PMCA in promoting calcium extrusion from astrocytes transformed by AD markers.