Cystic Fibrosis (CF) is an inherited disease associated with a variety of mutations affecting the CFTR gene. A deletion of phenylalanine 508 (F508) affects more than 70% of patients and results in unfolded proteins accumulation, originating a proteinopathy responsible for inflammation, impaired trafficking, altered metabolism, cholesterol and lipids accumulation, impaired autophagy at the cellular level. Lung inflammation has been extensively related to the accumulation of the lipotoxin ceramide. We recently proved that inhibition of ceramide synthesis by Myriocin reduces inflammation and ameliorates the defence response against pathogens infection, which is downregulated in CF. Here, we aim at demonstrating the mechanisms of Myriocin therapeutic effects in Cystic Fibrosis broncho-epithelial cells.

Inhibition of Sphingolipid Synthesis as a Phenotype-Modifying Therapy in Cystic Fibrosis / A. Mingione, M. Dei Cas, F. Bonezzi, A. Caretti, M. Piccoli, L. Anastasia, R. Ghidoni, R. Paroni, P. Signorelli. - In: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY. - ISSN 1015-8987. - 54:1(2020 Jan 31), pp. 110-125. [10.33594/000000208]

Inhibition of Sphingolipid Synthesis as a Phenotype-Modifying Therapy in Cystic Fibrosis

A. Mingione
Primo
;
M. Dei Cas
Secondo
;
F. Bonezzi;A. Caretti;M. Piccoli;L. Anastasia;R. Ghidoni;R. Paroni
Penultimo
;
P. Signorelli
Ultimo
2020-01-31

Abstract

Cystic Fibrosis (CF) is an inherited disease associated with a variety of mutations affecting the CFTR gene. A deletion of phenylalanine 508 (F508) affects more than 70% of patients and results in unfolded proteins accumulation, originating a proteinopathy responsible for inflammation, impaired trafficking, altered metabolism, cholesterol and lipids accumulation, impaired autophagy at the cellular level. Lung inflammation has been extensively related to the accumulation of the lipotoxin ceramide. We recently proved that inhibition of ceramide synthesis by Myriocin reduces inflammation and ameliorates the defence response against pathogens infection, which is downregulated in CF. Here, we aim at demonstrating the mechanisms of Myriocin therapeutic effects in Cystic Fibrosis broncho-epithelial cells.
Lipid metabolism; Ceramide; Proteinopathy; Autophagy; Cystic Fibrosis; Autophagy; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Line; Cholesterol; Chromatography, High Pressure Liquid; Cystic Fibrosis; Fatty Acids, Monounsaturated; Forkhead Box Protein O1; Humans; Lipid Metabolism; Mass Spectrometry; PPAR gamma; RNA Interference; RNA, Small Interfering; Serine C-Palmitoyltransferase; Sphingolipids; Sphingomyelins
Settore BIO/10 - Biochimica
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/723446
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