Details

Autor(en) / Beteiligte

• Puntoni, Mariarita
• Bigazzi, Federico
• Sabatino, Laura
• Sbrana, Francesco
• Musio, Antonio
• Dal Pino, Beatrice
• Ragusa, Andrea
• Corsano, Elena
• Sampietro, Tiziana

Titel

Early senescence in heterozygous ABCA1 mutation skin fibroblasts: A gene dosage effect beyond HDL deficiency?

Ist Teil von

• Biochemical and biophysical research communications, 2014-05, Vol.447 (2), p.231-236

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •ABCA1 gene mutation has a “gene dosage way” effect on in vitro fibroblast senescence.•Heterozygous ABCA1 mutation showed intermediate replicative senescent phenotype.•ABCG1 and LDLR gene expression could highlight a role of ABCA1 gene on cytoskeleton.•Further studies are needed to clarify the cellular dynamics in premature CAD. Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Hom), his father (Het), and in a healthy control might be induced in a “gene-dosage way”. Senescence was evaluated by staining test for β-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated. Hom cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for β-Galactosidase test was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Hom (p<0.0001) or in Het (p<0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary unit). ABCA1 gene mutation may have “gene-dosage way” effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism.