The gene seladin-1/DHCR24 (sel-1) codes for the enzyme that converts desmosterol to cholesterol. Its inactivating mutations leads to desmosterolosis, a disease characterised by several neurological defects. Sel-1 mRNA is downregulated in the brain regions more susceptible to the Alzheimer’s disease (AD); its expression is modulated by oxidative stress in non neuronal cells and linked with tumor progression, suggesting a role also in cell survival. This study set off to investigate the physiology of sel-1 in neuronal cells using immortalized mouse central neurons (GT1-7 and GN11 cell lines). The results show that sel-1 gene is expressed 100 fold higher in the mature GT1-7 neurons than in the immature GN11 neurons. We observed a partial colocalisation of sel-1 with the Golgi vesicles and the endoplasmic reticulum in both cell lines, and a localization in vesicles present near the axon terminals only in the mature GT1-7 neurons. Overexpression of the protein in the immature GN11 neurons by transfection with sel-1-GFP construct resulted in their morphological differentiation and a vesicular distribution similar to that of the mature neurons. By RT-PCR we found that sublethal induction of oxidative stress significantly downregulated sel-1 transcript in both GT1-7 and GN11 neurons; however this downregulation is accompanied with the appearance of an alternative longer transcript, suggesting the presence of a splicing variant of the gene. In conclusion, the results show that: a) sel-1 is differentially expressed and distributed in neuronal cells according to their maturational stage and b) the apparent decrease of sel-1 expression induced by oxidative stress might be due to an alternative splicing of the gene. (Grants: MIUR PRIN 2003060512_001; Fondazione CARIPLO)
SELADIN-1 AS A NEW EARLY MARKER FOR OXIDATIVE STRESS AND DEGENERATION IN CENTRAL NEURONS / A. Samara, M. Galbiati, R. Zaninetti, F. Piva, A. Peri, R. Maggi. - In: ACTA PHYSIOLOGICA. - ISSN 1748-1708. - 188:suppl. 652(2006), pp. 153-153. ((Intervento presentato al 56. convegno National Congress of the Italian Physiological Society tenutosi a Palermo (Italy) nel 2005.
|Titolo:||SELADIN-1 AS A NEW EARLY MARKER FOR OXIDATIVE STRESS AND DEGENERATION IN CENTRAL NEURONS|
|Parole Chiave:||DHCR24 ; cholesterol ; oxidative stress ; neurodegeneration ; ALzheimer|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1748-1716.2006.01617.x|
|Appare nelle tipologie:||01 - Articolo su periodico|