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Acta Physiologica 2009; Volume 197, Supplement 672
The 60th National Congress of the Italian Physiological Society
9/23/2009-9/25/2009
Siena, Italy
SELADIN-1/DHCR24 GENE OVEREXPRESSION DECREASED MIGRATION OF IMMATURE IMMORTALIZED NEURONS
Abstract number: OC-27
ORGANISTI1 C, SAMARA1 A, CARIBONI1 A, GALBIATI1 R, MAGGI1 R
1Dip. Endocrinologia, Fisiopatologia e Biologia Applicata e CIRMAR Univ. di Milano; (Italy)[email protected]
Aim:
DHCR24 (3beta-hydroxysterol delta24-reductase) is a key enzyme to form cholesterol from desmosterol; Interestingly, high levels of desmosterol are present during fetal brain development. DHCR24 is also called Seladin-1 (for Selective Alzheimer's Disease Indicator-1, Sel-1) since it is down-regulated in the brain regions more susceptible to this disease. Moreover, it has been implicated in tumor progression, neuroprotection and oxidative stress, suggesting a prosurvival and antiapoptotic action.
Methods:
In the present study we investigated the expression of Sel-1 in immortalized neurons derived from mature (GT1-7) and immature (GN11) endocrine neurons and a possible role in the neuronal maturation and motility.
Results:
We found that GT1-7 cells present 100 times higher levels of Sel-1 mRNA and protein compared to GN11 cells as well as a different intracellular distribution. Accordingly, an higher relative amount of desmosterol was present in GN11 cells. In a first series of functional experiments, we found that cyclodextrin-mediated membrane cholesterol/desmosterol substitution did not affect the motility of GN11 cells. By transfection of GN11 cells with a Seladin-1-GFP construct we observed an increase of the cholesterol and a decrease of the desmosterol content, a distribution of the protein similar to mature GT1-7 cells as well as a neurite growth stimulation. Moreover, by microchemotaxis assay, we found that transfected cells showed a decrease of their motility.
Conclusion:
In conclusions, these results are suggestive of a possible role of Seladin-1/DHCR24 on some event of neuronal development/differentiation, through a control of the intracellular cholesterol/desmosterol ratio.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 197, Supplement 672 :OC-27