Universität zu Köln

Staubach, Simon, Pekmez, Murat and Hanisch, Franz-Georg (2016). Differential Proteomics of Urinary Exovesicles from Classical Galactosemic Patients Reveals Subclinical Kidney Insufficiency. J. Proteome Res., 15 (6). S. 1754 - 1762. WASHINGTON: AMER CHEMICAL SOC. ISSN 1535-3907

Full text not available from this repository.

Abstract

Classical galactosemia is caused by a nearly complete deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), resulting in a severely impaired galactose metabolism with galactose-1-phosphate and galactitol accumulation. Even on a galactose-restricted diet, patients develop serious long-term complications of the central nervous system and ovaries that may result from chronic cell-toxic effects exerted by endogenous galactose. To address the question of whether disease-associated cellular perturbations could affect the kidney function of the patients, we performed differential proteomics of detergent-resistant membranes from urinary exovesicles. Galactosemic samples (showing drastic shifts from high-mannose to complex-type N-glycosylation on exosomal N-glycoproteins) and healthy, sex-matched controls were analyzed in quadruplex iTRAQ experiments performed in biological and technical replicates. Particularly in the female patient group, the most striking finding was a drastic increase of abundant serum (glyco)proteins, like albumin, leucine-rich alpha-2-glycoprotein, fetuin, immunoglobulins, prostaglandin H2 D-isomerase, and alpha-1-microglobulin protein (AMBP), pointing to a subclinical failure of kidney filter function in galactosemic patients and resulting in a heavy overload of exosomal membranes with adsorbed serum (glyco)proteins. Several of these proteins are connected to TBMN and IgAN, proteinuria, and renal damage. The impairment of renal protein filtration was also indicated by increased protein contents derived from extracellular matrices and lysosomes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Staubach, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Pekmez, Murat UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanisch, Franz-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-273617
DOI:	10.1021/acs.jproteome.5b00902
Journal or Publication Title:	J. Proteome Res.
Volume:	15
Number:	6
Page Range:	S. 1754 - 1762
Date:	2016
Publisher:	AMER CHEMICAL SOC
Place of Publication:	WASHINGTON
ISSN:	1535-3907
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SERUM TRANSFERRIN; EXOSOMES; IDENTIFICATION; NEPHROPATHY; BIOMARKER Multiple languages Biochemical Research Methods Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27361