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Mol Genet Metab. 2017 Jun;121(2):180-189. doi: 10.1016/j.ymgme.2017.04.006. Epub 2017 Apr 18.

Changes in Red Blood Cell membrane lipid composition: A new perspective into the pathogenesis of PKAN.

Author information

1
Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, 20126 Milan, Italy.
2
Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy.
3
IRBA, Unité des Risques Technologiques Emergeants BP 73, 91223 Brétigny sur Orge Cedex, France.
4
Unit of Clinical Pathology and Medical Genetics, Foundation IRCCS Neurological Institute C. Besta, Milan, Italy.
5
Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, United States.
6
Unit of Child Neurology, Foundation IRCCS Neurological Institute C. Besta, Milan, Italy.
7
Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy. Electronic address: angelamaria.rizzo@unimi.it.
8
Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, 20126 Milan, Italy. Electronic address: valeria.tiranti@istituto-besta.it.

Abstract

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). The PANK2 catalyzes the first step of coenzyme A (CoA) biosynthesis, a pathway producing an essential cofactor that plays a key role in energy and lipid metabolism. The majority of PANK2 mutations reduces or abolishes the activity of the enzyme. In around 10% of cases with PKAN, the presence of deformed red blood cells with thorny protrusions in the circulation has been detected. Changes in membrane protein expression and assembly during erythropoiesis were previously explored in patients with PKAN. However, data on red blood cell membrane phospholipid organization are still missing in this disease. In this study, we performed lipidomic analysis on red blood cells from Italian patients affected by PKAN with a particular interest in membrane physico-chemical properties. We showed an increased number of small red blood cells together with membrane phospholipid alteration, particularly a significant increase in sphingomyelin (SM)/phosphatidylcholine (PC) and SM/phosphatidylethanolamine (PE) ratios, in subjects with PKAN. The membrane structural abnormalities were associated with membrane fluidity perturbation. These morphological and functional characteristics of red blood cells in patients with PKAN offer new possible tools in order to shed light on the pathogenesis of the disease and to possibly identify further biomarkers for clinical studies.

KEYWORDS:

Biomarkers; Erythrocytes; Membrane; Mitochondria; NBIA; Neurodegenerative diseases; Oxidized lipids; PKAN; Phospholipids

PMID:
28456385
DOI:
10.1016/j.ymgme.2017.04.006
[Indexed for MEDLINE]

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