Expression of a Second Ecto-5′-Nucleotidase Variant Besides the Usual Protein in Symptomatic Phase of Experimental Autoimmune Encephalomyelitis

Abstract Ecto-5′-nucleotidase/cluster of differentiation 73 (CD73) (eN) is a 70-kDa glycoprotein expressed in several different mammalian tissues and cell types. It is the rate-limiting enzyme of the purine catabolic pathway, which catalyzes the hydrolysis of AMP to produce adenosine with known anti-inflammatory and immunosuppressive actions. There is strong evidence for lymphocyte and endothelial cell eN having a role in experimental autoimmune encephalomyelitis (EAE), but the role of eN in cell types within the central nervous system is less clear. We have previously shown that eN activity significantly increased in the lumbar spinal cord during EAE. The present study is aimed to explore molecular pattern of the eN upregulation over the course of the disease and cell type(s) accountable for the induction. EAE was induced in Dark Agouti (DA) rats by immunization with the spinal cord tissue homogenate and adjuvant. Animals were sacrificed 8, 15, and 28 days following immunization (D8, D15, and D28), i.e., at time points which corresponded to the presymptomatic, symptomatic, and postsymptomatic phases of the disease, respectively. Significant increase in eN activity and its upregulation at the gene and the protein levels were demonstrated at D15 and less prominently at D28 in comparison to control. Additionally, reactive astrocytes abundantly present in the lumbar spinal cord parenchyma were identified as principal cell type with significantly elevated eN expression. In all experimental groups, eN was expressed as a 71-kDa protein band of uniform abundance, whereas the overexpression of eN at D15 and D28 was associated with the expression of a second 75-kDa eN variant. The possible outcome of eN upregulation during EAE as a part of protective astrocyte repertoire contributing to the resolution of the disease is discussed..

Medienart:	E-Artikel

Erscheinungsjahr:	2014
Erschienen:	2014

Enthalten in:	Zur Gesamtaufnahme - volume:55
Enthalten in:	Journal of molecular neuroscience - 55(2014), 4 vom: 19. Okt., Seite 898-911

Sprache:	Englisch

Beteiligte Personen:	Lavrnja, Irena [VerfasserIn] Laketa, Danijela [VerfasserIn] Savic, Danijela [VerfasserIn] Bozic, Iva [VerfasserIn] Bjelobaba, Ivana [VerfasserIn] Pekovic, Sanja [VerfasserIn] Nedeljkovic, Nadezda [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

BKL:	44.90
Themen:	Adenosine Astrocytes EAE Ecto-5′-nucleotidase/CD73 Glycosylation Neuroinflammation

doi:	10.1007/s12031-014-0445-x

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	SPR023852852