Phosphorylation and Dephosphorylation of Beta-Amyloid Peptide in Model Cell Cultures: The Role of Cellular Protein Kinases and Phosphatases.

Autor: Barykin EP; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Yanvarev DV; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Strelkova MA; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Valuev-Elliston VT; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Varshavskaya KB; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Mitkevich VA; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia., Makarov AA; Engelhardt Institute of Molecular Biology, Vavilov Str. 32, 119991 Moscow, Russia.
Jazyk: angličtina
Zdroj: Life (Basel, Switzerland) [Life (Basel)] 2023 Jan 04; Vol. 13 (1). Date of Electronic Publication: 2023 Jan 04.
DOI: 10.3390/life13010147
Abstrakt: Phosphorylation of beta-amyloid peptide (Aβ) at the Ser8 residue affects its neurotoxicity, metal-dependent oligomerisation, amyloidogenicity, and other pathogenic properties. Phosphorylated Aβ (pS8-Aβ) was detected in vivo in AD model mice and in the brains of patients with AD. However, the pS8-Aβ production and the regulation of its levels have not been previously studied in detail. In this paper, immunochemical methods together with radioactive labelling were used to study the Aβ phosphorylation by intracellular and surface protein kinases of HEK293 cells and brain endothelial cells (bEnd.3). It was found that HEK293 robustly phosphorylated Aβ, likely with contribution from casein kinase 2 (CK2), whereas in bEnd.3, the activity of Aβ phosphorylation was relatively low. Further, the study showed that both HEK293 and bEnd.3 could dephosphorylate pS8-Aβ, mainly due to the activity of protein phosphatases PP1 and PP2A. The Aβ dephosphorylation efficiency in bEnd.3 was three times higher than in HEK293, which correlated with the reduced abundance of pS8-Aβ in vascular amyloid deposits of patients with AD compared to senile plaques. These data suggest an important role of CK2, PP1, and PP2A as regulators of Aβ phosphorylation, and point to the involvement of the blood-brain barrier in the control of Aβ modification levels.
Databáze: MEDLINE
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