Acylphosphatase overexpression triggers SH-SY5Y differentiation towards neuronal phenotype

Cellular and Molecular Life Sciences : CMLS
C CecchiG Ramponi

Abstract

An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y neuroblastoma cells, using a green fluorescent fusion protein (AcP-GFP), with GFP acting as a reporter protein. The cellular proliferation rate was significantly reduced by overexpression of AcPase by a factor of ten. In contrast, clones transfected with two inactive AcPase mutants showed a growth rate comparable to control cells. This suggests that AcPase catalyzes the proliferative down-regulation. AcPase-overexpressing clones showed a physiological mortality rate as assessed by an MTT reduction test and by evaluation of necrotic markers. DNA fragmentation analysis and assays of caspase-3 and poly (ADP-ribose) polymerase (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase overexpression led to a marked increase in PARP activity as well as Bcl-2 content; these are commonly up-regulated during differentiative processes in neuronal cells. In fact, the typical differentiation marker, growth-associated-protein 43, was significantly up-regulated. Microscopic observations also showed a clear increase in the differentiative phenotype in AcPase-overexpressing cells. Our results clearly show that AcPase plays a primary causative role in ...Continue Reading

Citations

Feb 24, 2007·Differentiation; Research in Biological Diversity·Ji Won KimMyoung Hee Kim
Oct 7, 2017·The Journal of Gene Medicine·Ying CuiShijie Mu
May 14, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ling ChengKaren M Harnett
Sep 6, 2019·Molecular Genetics & Genomic Medicine·Yuhe WangTianbo Jin

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