Hypoxia induces up-regulation of progranulin in neuroblastoma cell lines

Progranulin (PGRN) is a widely expressed multifunctional protein involved in regulation of cell growth and cell cycle progression with a possible involvement in neurodegeneration We looked for PGRN regulation in three different human neuroblastoma cell lines following exposure to two different stimuli commonly associated to neurodegeneration hypoxia and oxidative stress For gene and protein expression analysis we carried out a quantitative RT-PCR and western blotting analysis We show that PGRN is strongly up-regulated by hypoxia through the mitogen-actived protein kinase (MAPK)/extracellular signal-regulated kinase (MEK) signaling cascade PGRN is not up-regulated by H2O2-induced oxidative stress These results suggest that PGRN in the brain could exert a protective role against hypoxic stress one of principal risk factors involved in frontotemporal dementia pathogenesis (C) 2010 Elsevier Ltd All rights reserved