CIDIE   24052
CENTRO DE INVESTIGACION Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Regulation of the sphingolipid metabolism by malondialdehyde-acetaldehyde protein adducts and complement regulators in human retinal cell lines
Autor/es:
LIN, YUCHEN; WEBER, BERNHARD H. F.; PUJOL LEREIS, LUCIANA M.; LIEBISCH, GERHARD; ZIPFEL, PETER F.; SKERKA, CHRISTINE
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
We previously reported increased levels of serum ceramides in patients with age-related macular degeneration (AMD), a common sight-threatening condition with complex etiology. We observed that genetic variant rs1061170 (p.Y402H) in the complement factor H (CFH)/factor H-like protein 1 (FHL-1) gene correlates with Cer d18:1/16:0 levels in AMD. The aim of this study was to evaluate the cellular sphingolipid metabolism under treatment with malondialdehyde-acetaldehyde (MAA) adducts, a product of oxidative stress shown to be highly elevated in AMD retinas, and the modulation by FHL-1, an alternative splicing isoform of CFH. Gene expression, survival and sphingolipid levels were evaluated in WERI-Rb1 and ARPE-19 cells exposed to MAA-BSA or BSA (control). We evaluated the influence of FHL-1 and CFH on gene expression by quantitative RT-PCR. Lipids were quantified by electrospray ionization tandem mass spectrometry (ESI-MS/MS), and cell survival was estimated by the MTT assay. Data statistics were done by t-tests or ANOVAs. The expression of SMPD2 and SMPD3 which are involved in the synthesis of sphingomyelin (SM) from ceramide decreased with addition of MAA-BSA in ARPE-19 cells (p