Ceruloplasmin‐deficient mice show changes inPTMprofiles of proteins involved in messengerRNAprocessing and neuronal projections and synaptic processes

Abstract

Ceruloplasmin (Cp) is a multicopper oxidase with ferroxidase properties being of importance to the mobilisation and export of iron from cells and its ability to bind copper. In ageing humans, Cp deficiency is known to result in aceruloplasminemia, which among other is characterised by neurological symptoms. To obtain novel information about the functions of Cp in the central nervous system (CNS) we compared the brain proteome in forebrains from asymptomatic 4‐6‐month‐old Cp‐deficient (B6N(Cg)‐Cptm1b(KOMP)Wtsi/J) and wild‐type mice. Of more than 5600 quantified proteins, 23 proteins, were regulated, whereas more than 1200 proteins had regulated post‐translational modifications (PTMs). The genes of the regulated proteins, glycoproteins and phosphoproteins appeared mostly to be located to neurons and oligodendrocyte precursor cells. Cp deficiency especially affected the function of proteins involved in the extension of neuronal projections, synaptic signalling and cellular mRNA processing and affected the expression of proteins involved in neurodegenerative disease and diabetes. Iron concentration and transferrin saturation were reduced in the blood of even younger, 3‐ to 5‐month‐old, Cp‐deficient mice. Iron act as cofactor in many enzymatic processes and reactions. Changes in iron availability and oxidation as consequence of Cp deficiency could therefore affect the synthesis of proteins and lipids. This proteomic characterisation is to our knowledge the first to document the changes taking place in the CNS‐proteome and its phosphorylation and glycosylation state in Cp‐deficient mice.

Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma

“…Besides, CP plays a more prominent role in iron uptake than release ( Mukhopadhyay et al, 2000 ; Mietto et al, 2021 ). Some recent studies stated that the abnormal CP expression occurring in the brain could be attributed to a few neurological diseases ( Klomp and Gitlin, 1996 ; Qian and Ke, 2019 ; Villadsen et al, 2023 ). At present, the existing literature studies have reported that in the iron-deficient and iron-saturated cells, CP, regardless of concentration, promotes the uptake of transferrin-bound iron and ferric citrate by glioma cells ( Attieh et al, 1999 ; Roy et al, 2022 ).…”