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神经毒性淀粉样β肽和tau对胶质母细胞瘤细胞系中的质膜钙泵产生细胞因子样作用，增强其活性和异构体表达。

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

作者信息

Berrocal María, Alvarez-Barrientos Alberto, Mata Ana M

机构信息

Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.

Instituto de Biomarcadores de Patologías Moleculares (IBPM), Universidad de Extremadura, Badajoz, Spain.

出版信息

FEBS Open Bio. 2025 Aug;15(8):1350-1364. doi: 10.1002/2211-5463.70046. Epub 2025 May 5.

DOI:10.1002/2211-5463.70046
PMID:40325855
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12319713/
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 Ca-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.

摘要

炎症细胞因子可将星形胶质细胞转变为神经毒性反应性星形胶质细胞（分类为A1型），且它们与脑损伤和神经退行性疾病的关联已被广泛记录。然而，在星形胶质细胞中，阿尔茨海默病（AD）的两种生物标志物——淀粉样β肽（Aβ）和tau蛋白，以及参与钙稳态微调的钙泵的作用，目前仍知之甚少。在本研究中，我们发现用细胞因子混合物处理星形细胞瘤U - 251细胞可显著增加质膜钙ATP酶（PMCA）的活性以及四种PMCA亚型的表达水平。此外，用Aβ1 - 42或tau蛋白处理细胞会诱导PMCA活性和亚型表达水平出现与细胞因子类似的上调。这些效应支持了Aβ和tau与炎症的密切关联。本研究可能有助于更好地理解PMCA在促进由AD标志物转化的星形胶质细胞钙外排中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/0fd57b736c16/FEB4-15-1350-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/bbd49e703efc/FEB4-15-1350-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/0fd57b736c16/FEB4-15-1350-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/d3fdcf23cef3/FEB4-15-1350-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/21186d7ecb5b/FEB4-15-1350-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/a5886d873146/FEB4-15-1350-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/dc142666bca7/FEB4-15-1350-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/7d855024f37c/FEB4-15-1350-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/bbd49e703efc/FEB4-15-1350-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb40/12319713/0fd57b736c16/FEB4-15-1350-g001.jpg

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本文引用的文献

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Store-Operated Calcium Entry Inhibition and Plasma Membrane Calcium Pump Upregulation Contribute to the Maintenance of Resting Cytosolic Calcium Concentration in A1-like Astrocytes.
钙库操纵性钙内流抑制和质膜钙泵上调有助于维持 A1 样星形胶质细胞内的静息细胞浆钙离子浓度。
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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease.星形胶质细胞反应影响了淀粉样蛋白-β对临床前阿尔茨海默病中 tau 病理的影响。
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