Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered p
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ORIGINAL ARTICLE
Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis Nicoletta Loberto 1 & Giulia Mancini 1 & Rosaria Bassi 1 & Emma Veronica Carsana 1 & Anna Tamanini 2 & Nicoletta Pedemonte 3 & Maria Cristina Dechecchi 4 & Sandro Sonnino 1 & Massimo Aureli 1 Received: 23 May 2020 / Revised: 30 June 2020 / Accepted: 6 July 2020 # The Author(s) 2020
Abstract Human primary bronchial epithelial cells differentiated in vitro represent a valuable tool to study lung diseases such as cystic fibrosis (CF), an inherited disorder caused by mutations in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator. In CF, sphingolipids, a ubiquitous class of bioactive lipids mainly associated with the outer layer of the plasma membrane, seem to play a crucial role in the establishment of the severe lung complications. Nevertheless, no information on the involvement of sphingolipids and their metabolism in the differentiation of primary bronchial epithelial cells are available so far. Here we show that ceramide and globotriaosylceramide increased during cell differentiation, whereas glucosylceramide and gangliosides content decreased. In addition, we found that apical plasma membrane of differentiated bronchial cells is characterized by a higher content of sphingolipids in comparison to the other cell membranes and that activity of sphingolipids catabolic enzymes associated with this membrane results altered with respect to the total cell activities. In particular, the apical membrane of CF cells was characterized by high levels of ceramide and glucosylceramide, known to have proinflammatory activity. On this basis, our data further support the role of sphingolipids in the onset of CF lung pathology. Keywords Primary cells . Bronchial cells . Sphingolipids . Hydrolases . Membrane domains . Cystic fibrosis . CFTR
Introduction Nicoletta Loberto and Giulia Mancini contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10719-020-09935-x) contains supplementary material, which is available to authorized users. * Massimo Aureli [email protected] 1
Dip. Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, Segrate, Milano 20090, Italy
2
Section of Molecular Pathology, Department of Pathology and Diagnostics, University Hospital of Verona, 37126 Verona, Italy
3
U.O.C. Genetica Medica, IRCCS Giannina Gaslini, 16147 Genova, Italy
4
Section of Clinical Biochemistry, Department of Neurosciences, Biomedicine and Movement, University of Verona, 37134 Verona, Italy
Sphingolipids (SLs) are bioactive lipids asymmetrically distributed at the external leaflet of the plasma membrane (PM) of all eukaryotic cells. They are characterized by a hydrophilic head group protruding toward the extracellular environment and by ceramide (Cer) a peculiar lipid moiety, deeply inserted into the membrane bila
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