title: Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?
abstract: 24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration.
authors.affiliation: Dipartimento di Biologia, Università di Napoli Federico II, via Mezzocannone 8, 80134 Napoli, Italy. Electronic address: valeria.lamarca@gmail.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: La Marca
authors.affiliation: Dipartimento di Biologia, Università di Napoli Federico II, via Mezzocannone 8, 80134 Napoli, Italy. Electronic address: b.maresca@libero.it.
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Maresca
authors.affiliation: Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo (ISPAAM), Consiglio Nazionale delle Ricerche, via Argine 1085, 80147 Napoli, Italy. Electronic address: mariastefania.spagnuolo@cnr.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Spagnuolo
authors.affiliation: Dipartimento di Biologia, Università di Napoli Federico II, via Cinthia 4, 80126 Napoli, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPEB), via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: luisa.cigliano@unina.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cigliano
authors.affiliation: Dipartimento di Farmacia, Università di Salerno, via Giovanni Paolo II 132, 84084 Fisciano, Italy. Electronic address: fdalpiaz@unisa.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.affiliation: Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Seconda Università di Napoli, Piazza Miraglia 2, 80138 Napoli, Italy. Electronic address: giuseppe.diiorio@unina2.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Iorio
authors.affiliation: Dipartimento di Biologia, Università di Napoli Federico II, via Mezzocannone 8, 80134 Napoli, Italy; Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPEB), via Mezzocannone 16, 80134 Napoli, Italy. Electronic address: paolo.abrescia@unina.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Abrescia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001253:Astrocytes / Q000201:enzymology; D001921:Brain / Q000201:enzymology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004951:Esterification; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: 24-Hydroxycholesterol; Amyotrophic lateral sclerosis; Cerebrospinal fluid; Human neuroblastoma cell line SH-SY5Y; Lecithin-cholesterol acyltransferase; Oxidative stress